Anoectochilus roxburghii polysaccharide reduces D-GalN/LPS-induced acute liver injury by regulating the activation of multiple inflammasomes.

BACKGROUND: Acute liver injury (ALI) is a serious syndrome with a high mortality rate due to viral infection, toxic exposure, and autoimmunity, and its severity can range from mildly elevated liver enzymes to severe liver failure. Activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is closely associated with the development of ALI, and the search for an inhibitor targeting this pathway may be a novel therapeutic option. Anoectochilus roxburghii polysaccharide (ARP) is a biologically active ingredient extracted from Anoectochilus roxburghii with immunomodulatory, antioxidant, and anti-inflammatory bioactivities and pharmacological effects. In this study, we focused on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury by ARP through inhibition of NLRP3 inflammasome. METHODS: An inflammasome activation model was established in bone marrow-derived macrophages (BMDMs) to investigate the effects of ARP on caspase-1 cleavage, IL-1ß secretion, and ASC oligomerization in inflammasomes under different agonists. We used the D-GalN/LPS-induced acute liver injury model in mice, intraperitoneally injected ARP or MCC950, and collected liver tissues, serum, and intraperitoneal lavage fluid for pathological and biochemical indexes. RESULTS: ARP effectively inhibited the activation of the NLRP3 inflammasome and had an inhibitory effect on non-classical NLRP3, AIM2, and NLRC4 inflammasomes. It also effectively inhibited the oligomerization of apoptosis-associated speck-like protein (ASC) from a variety of inflammatory vesicles. Meanwhile, ARP has good therapeutic effects on acute liver injury induced by D-GaIN/LPS. CONCLUSION: The inhibitory effect of ARP on a wide range of inflammasomes, as well as its excellent protection against acute liver injury, suggests that ARP may be a candidate for acute liver injury.

Glabridin improves autoimmune disease in Trex1-deficient mice by reducing type I interferon production.

BACKGROUND: The cGAS-STING signaling pathway is an essential section of the natural immune system. In recent years, an increasing number of studies have shown a strong link between abnormal activation of the cGAS-STING signaling pathway, a natural immune pathway mediated by the nucleic acid receptor cGAS, and the development and progression of autoimmune diseases. Therefore, it is important to identify an effective compound to specifically downregulate this pathway for disease. METHODS: The effect of Glabridin (Glab) was investigated in BMDMs and Peripheral blood mononuclear cell (PBMC) by establishing an in vitro model of cGAS-STING signaling pathway activation. An activation model stimulated by DMXAA was also established in mice to study the effect of Glab. On the other hand, we investigated the possible mechanism of action of Glab and the effect of Glab on Trex1-deficient mice. RESULTS: In this research, we report that Glab, a major component of licorice, specifically inhibits the cGAS-STING signaling pathway by inhibiting the level of type I interferon and inflammatory cytokines (IL-6 and TNF-α). In addition, Glab has a therapeutic effect on innate immune diseases caused by abnormal cytoplasmic DNA in Trex1-deficient mice. Mechanistically, Glab can specifically inhibit the interaction of STING with IRF3. CONCLUSION: Glab is a specific inhibitor of the cGAS-STING signaling pathway and may be used in the clinical therapy of cGAS-STING pathway-mediated autoimmune diseases.

Transnasal humidified rapid-insufflation ventilator exchange compared with laryngeal mask airway for endoscopic thoracic sympathectomy: a randomized controlled trial.

Background: Transnasal humidified rapid-insufflation ventilator exchange (THRIVE) has the characteristics of operating easily and maintaining oxygenation and eliminating CO2, which makes it possible to be used in endoscopic thoracic sympathectomy (ETS). The application of THRIVE in ETS remains undefined. The purpose of this randomized controlled study is to assess the efficacy between THRIVE and laryngeal mask airway (LMA) for ETS. Methods: In total, 34 patients from May 2022 to May 2023 in Huazhong University of Science and Technology Union Shenzhen Hospital undergoing ETS were randomly divided into a THRIVE group (n = 17) and an LMA group (n = 17). A serial arterial blood gas analysis was conducted during the perioperative period. The primary outcome was the arterial partial pressure of carbon dioxide (PaCO2) during the perioperative period. The secondary outcome was arterial partial pressure of oxygen (PaO2) during the perioperative period. Results: The mean (SD) highest PaCO2 in the THRIVE group and LMA group were 99.0 (9.0) mmHg and 51.7 (5.2) mmHg, respectively (p < 0.001). The median (inter-quartile range) time to PaCO2 ≥ 60 mmHg in the THRIVE group was 26.0 min (23.2-28.8). The mean (SD) PaO2 was 268.8 (89.0) mmHg in the THRIVE group and 209.8 (55.8) mmHg in the LMA group during surgery (p = 0.027). Conclusion: CO2 accumulation in the THRIVE group was higher than that of the LMA group during ETS, but THRIVE exhibited greater oxygenation capability compared to LMA. We preliminarily testified that THRIVE would be a feasible non-intubated ventilation technique during ETS under monitoring PaCO2.

Extraction of soybean plant trait parameters based on SfM-MVS algorithm combined with GRNN.

Soybean is an important grain and oil crop worldwide and is rich in nutritional value. Phenotypic morphology plays an important role in the selection and breeding of excellent soybean varieties to achieve high yield. Nowadays, the mainstream manual phenotypic measurement has some problems such as strong subjectivity, high labor intensity and slow speed. To address the problems, a three-dimensional (3D) reconstruction method for soybean plants based on structure from motion (SFM) was proposed. First, the 3D point cloud of a soybean plant was reconstructed from multi-view images obtained by a smartphone based on the SFM algorithm. Second, low-pass filtering, Gaussian filtering, Ordinary Least Square (OLS) plane fitting, and Laplacian smoothing were used in fusion to automatically segment point cloud data, such as individual plants, stems, and leaves. Finally, Eleven morphological traits, such as plant height, minimum bounding box volume per plant, leaf projection area, leaf projection length and width, and leaf tilt information, were accurately and nondestructively measured by the proposed an algorithm for leaf phenotype measurement (LPM). Moreover, Support Vector Machine (SVM), Back Propagation Neural Network (BP), and Back Propagation Neural Network (GRNN) prediction models were established to predict and identify soybean plant varieties. The results indicated that, compared with the manual measurement, the root mean square error (RMSE) of plant height, leaf length, and leaf width were 0.9997, 0.2357, and 0.2666 cm, and the mean absolute percentage error (MAPE) were 2.7013%, 1.4706%, and 1.8669%, and the coefficients of determination (R2) were 0.9775, 0.9785, and 0.9487, respectively. The accuracy of predicting plant species according to the six leaf parameters was highest when using GRNN, reaching 0.9211, and the RMSE was 18.3263. Based on the phenotypic traits of plants, the differences between C3, 47-6 and W82 soybeans were analyzed genetically, and because C3 was an insect-resistant line, the trait parametes (minimum box volume per plant, number of leaves, minimum size of single leaf box, leaf projection area).The results show that the proposed method can effectively extract the 3D phenotypic structure information of soybean plants and leaves without loss which has the potential using ability in other plants with dense leaves.

Association between diabetes status and breast cancer in US adults: findings from the US National Health and Nutrition Examination Survey.

Objectives: The aim of this study was to investigate the association between diabetes status and the risk of breast cancer among adult Americans, exploring the impact of BMI, age, and race on this relationship. Methods: A cross-sectional analysis of 8,249 individuals from the National Health and Nutrition Examination Survey (NHANES) was conducted. Diabetes was categorized as type 2 diabetes and prediabetes, with both conditions diagnosed according to the ADA 2014 guidelines. The association between diabetes status and breast cancer risk was explored using multiple logistic regression analysis. Results: Patients with diabetes had higher odds of breast cancer (OR: 1.51; 95% CI 1.00 to 2.28), Using the two-piecewise linear regression model, it was observed that there is a threshold effect in the risk of breast cancer occurrence at the age of 52 years. Specifically, the risk of breast cancer is relatively low before the age of 52 but increases significantly after this age. Conclusions: This study identified a significant association between diabetes status and breast cancer risk among adult Americans. We also found a threshold effect in breast cancer occurrence at the age of 52. Age was significantly associated with breast cancer risk in both Non-Hispanic White and Non-Hispanic Black individuals. These findings underscore the importance of diabetes management, maintaining a healthy BMI, and age-related risk considerations in reducing breast cancer risk.

Association of Combined Exposure to Ambient Air Pollutants, Genetic Risk, and Incident Rheumatoid Arthritis: A Prospective Cohort Study in the UK Biobank.

BACKGROUND: Evidence for a potential link between air pollution and rheumatoid arthritis (RA) is inconsistent, and the modified effect of genetic susceptibility on the relationship between air pollution and RA has not been well studied. OBJECTIVE: Using a general population cohort from the UK Biobank, this study aimed to investigate the associations between various air pollutants and the risk of incident RA and to further estimate the impact of combined exposure to ambient air pollutants on the risk of developing RA under the modification effect of genetic predisposition. METHODS: A total of 342,973 participants with completed genotyping data and who were free of RA at baseline were included in the study. An air pollution score was constructed by summing the concentrations of each pollutant weighted by the regression coefficients with RA from single-pollutant models to assess the combined effect of air pollutants, including particulate matter (PM) with diameters ≤2.5µm (PM2.5), between 2.5 and 10µm (PM2.5-10), and ≤10µm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). In addition, the polygenic risk score (PRS) of RA was calculated to characterize individual genetic risk. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of associations of single air pollutant, air pollution score, or PRS with incident RA. RESULTS: During a median follow-up time of 8.1 y, 2,034 incident events of RA were recorded. The HRs (95% CIs) of incident RA per interquartile range increment in PM2.5, PM2.5-10, PM10, NO2, and NOx were 1.07 (1.01, 1.13), 1.00 (0.96, 1.04), 1.01 (0.96, 1.07), 1.03 (0.98, 1.09), and 1.07 (1.02, 1.12), respectively. We also found a positive exposure-response relationship between air pollution score and RA risk (pTrend=0.000053). The HR (95% CI) of incident RA was 1.14 (1.00, 1.29) in the highest quartile group compared with the lowest quartile group of the air pollution score. Furthermore, the results of the combined effect of air pollution score and PRS on the RA risk showed that the risk of RA incidence in the highest genetic risk and air pollution score group was almost twice that of the lowest genetic risk and air pollution score group [incidence rate (IR) per 100,000 person-years: 98.46 vs. 51.19, and HR= 1.73 (95% CI: 1.39, 2.17) vs. 1 (reference)], although no statistically significant interaction between the air pollution and genetic risk for incident RA was found (pInteraction>0.05). DISCUSSION: The results revealed that long-term combined exposure to ambient air pollutants might increase the risk of RA, particularly in those with high genetic risk. https://doi.org/10.1289/EHP10710.

Short-term effect of ambient temperature and ambient temperature changes on the risk of warts outpatient visits in Hefei, China: a retrospective time-series study.

Concerns are growing about the adverse health effects of ambient temperature and ambient temperature changes. However, the association between ambient temperature and ambient temperature changes on the risk of warts outpatient visits is poorly understood. Our study used the distributed lag non-linear model (DLNM) aimed to evaluate the association between ambient temperature, ambient temperature changes (including temperature change between neighboring days (TCN) and diurnal temperature range (DTR)), and warts outpatient visits. We also performed subgroup analyses in order to find susceptible populations by gender and age groups. The maximum relative risk (RR) of low ambient temperature (0 °C) for warts outpatient visits was 1.117 (95% CI: 1.041-1.198, lag 04 days), and the maximum RR of high ambient temperature (32 °C) for warts outpatient visits was 1.318 (95% CI: 1.083-1.605, lag 07 days). The large temperature drop (TCN = - 3 °C) decreased the risk of warts visits, with the lowest RR value at the cumulative exposure of lag 7 days (RR = 0.888, 95% CI: 0.822-0.959), and the large temperature rise (TCN = 2 °C) increased the risk of warts visits, with the highest RR value at the cumulative exposure of lag 7 days (RR = 1.080, 95% CI: 1.022-1.142). Overall, both low and high ambient temperatures and large temperature rise can increase the risk of warts visits, while large temperature drop is a protective factor for warts visits. However, we did not find any association between DTR and warts visits. Furthermore, subgroup analyses showed that males and the young (0-17 years old) were more sensitive to low and high ambient temperatures, and the elderly (≥ 65 years old) were more susceptible to TCN. The results may provide valuable evidence for reducing the disease burden of warts in the future.

Evaluation of Rearing Factors Affecting Clanis bilineata tsingtauica Mell Larvae Fed by Susceptible Soybean Variety NN89-29 in Spring and Autumn Sowing.

Clanis bilineata tsingtauica Mell is a nutritious edible insect. In the present study, soybean variety NN89-29 susceptible to leaf-feeding insects was used as the experiment material to evaluate the rearing factors affecting the production of C. bilineata tsingtauica in spring and autumn sowing. We artificially inoculated C. bilineata tsingtauica eggs to soybean plants, and the relevant indexes of larvae and soybean plants were recorded. The main results from spring sowing were as follows: (1) Larval number, single larval weight and plot-larval weight were all higher in the V6 stage (sixth trifoliolate) than those in the R3 stage (beginning pod) of inoculated eggs. (2) Larval number, single larval weight and plot-larval weight significantly decreased under higher planting density. Meanwhile, the soybean plant height and internode length increased, while the main stem node number of soybean decreased under higher planting density. (3) Single larval weight and plot-larval weight were not significantly affected by different numbers of eggs inoculated, but the larval number was significantly affected. Under autumn sowing conditions: (1) The larvae production and soybean plant growth were not significantly affected by covering the top of the net house with plastic film to isolate rainwater. (2) More eggs inoculated were associated with higher plot-larval weight. Conversely, fewer eggs inoculated resulted in a higher proportion of single larvae weight more than or equal to 6 g (≥6 g). Compared to spring sowing, the low biomass of autumn-sown soybean plants did not provide sufficient food for C. bilineata tsingtauica growth, and competition for food resulted in lower larval number, single larval weight and plot-larval weight.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Increased microneedle-mediated transdermal delivery of tetramethylpyrazine to the brain, combined with borneol and iontophoresis, for MCAO prevention.

The aim of this research was to improve transdermal delivery and distribution of tetramethylpyrazine (TMP) in the brain, by adding borneol (BN) and iontophoresis (ITP), and using microneedles (MN), to prevent middle cerebral artery occlusion (MCAO). BN was encapsulated into sulfobutylated-ß-cyclodextrin (BN-SBE-ß-CD), and then dispersed together with TMP. Four delivery groups were tested: passive (with no ITP and MN), ITP, MN, and MN combined with ITP (MN-ITP). In vitro transdermal fluxes of the drugs in those groups and in that corresponding order were 79.12 ± 14.5, 395.43 ± 12.37, 319.16 ± 29.99, and 1018.07 ± 108.92 µg/cm2 (for TMP), and 39.34 ± 1.31, 202.81 ± 53.56, 715.47 ± 75.52, and 1088.60 ± 53.90 µg/cm2 (for BN), respectively, which indicated that the use of MN-ITP greatly enhanced transdermal TMP and BN delivery compared to the other groups. The AUC0-t for the combined use of TMP and BN drugs was measured using two in vivo studies, cutaneous microdialysis and pharmacodynamic, yielding increased folds of 3.69 and 1.98 in ITP, 6.05 and 2.73 in MN, and 12.43 and 7.47 in MN-ITP groups, respectively, as compared to those in the passive group. In addition, the combined use of TMP and BN increased TMP distribution in the heart and the brain, indicated by TMP Cmax of 1.76- and 1.59-fold higher (p < 0.05), and TMP AUC0-t of 1.50 times and 1.19-fold higher (p < 0.01), than with administration of TMP in absence of BN, respectively. The brain infarction area and IL-ß expression in the MCAO rat were significantly decreased in the MN-ITP group, compared with the control group (p < 0.05). In conclusion, combination of MN and ITP resulted in a synergistic enhancement of transdermal delivery and distribution of TMP in the brain, when in combination with BN, thereby significantly decreasing the infarct volumes and improving the neurological scores of MCAO.

Construction and in vitro and in vivo evaluation of folic acid-modified nanostructured lipid carriers loaded with paclitaxel and chlorin e6.

Breast cancer remains a major threat to women's health, and the incidence of breast cancer continues to increase each year. Paclitaxel (PTX) is commonly used to treat breast cancer, but shows limited solubility and is associated with major side effects, limiting its clinical applications. Photodynamic therapy (PDT) is a promising treatment for breast cancer but is limited by the poor solubility of photosensitizers and difficulties in targeting and enriching the tumor tissue with photosensitizers. Here, we prepared a new nanocarrier system using nanostructured lipid carriers (PTX@FA-NLC-PEG-Ce6) harboring PTX, chlorin e6 (Ce6), and folic acid-targeted head to overcome the limitations of PTX and Ce6 in hydrophobicity and increase the target efficiency of chemotherapy drugs and photosensitizers at the tumor. The results showed that the drug-loading system met the requirements for intravenous injection, had tumor targeting ability, and could be easily taken up by MDA-MB-231 cells. Moreover, Ce6 could be dissociated from the surface of the drug-loading system and evenly distributed in cells after a period of time when the nanostructured lipid carriers had entered lysosomes through endocytosis. Additionally, reactive oxygen species were then produced to induce PDT at a specific wavelength of illumination. In vitro pharmacodynamic experiments showed that combined PDT and chemotherapy had synergistic effects (combination index: 0.647). Furthermore, pharmacodynamic experiments in nude mice showed that the drug-loading system had ideal antitumor effects without obvious side effects. Thus, PTX@FA-NLC-PEG-Ce6 may have applications as a promising drug-loading system for PDT combined with chemotherapy in patients with breast cancer.

Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system.

In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine (TMP) is enhanced when combined with borneol (BN) in a microemulsion-based transdermal therapeutic system (ME-TTS). The formulation of the TMP and BN microemulsion (TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher (P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group (P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

PURPOSE: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. METHODS: OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. RESULTS: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. CONCLUSION: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.