Unique attributes of official endorsers in destination marketing.

Along with the digital transformation of the administrative environment and the end of the COVID-19 pandemic, official endorsers have nurtured a new channel for tourism destination marketing, which is of great significance to local economic recovery. However, less attention has been paid to the different effects of endorsement between ordinary endorsers and official endorsers, mainly due to their contrasting social statuses. To bridge the research gap, the source credibility model and social identity theory are integrated to construct the distinctive attributes of officials, as well as structural equation model is utilized to explore the underlying mechanism of official endorsement. Findings indicate that trustworthiness, the sense of authority, expertise, and attractiveness have direct positive effects on official identification, while also indirectly influencing tourists' attitudes toward the destination through official identification. These findings provide theoretical and managerial implications for the local government managers involved in tourism destination marketing.

Res2Net-based multi-scale and multi-attention model for traffic scene image classification.

With the increasing applications of traffic scene image classification in intelligent transportation systems, there is a growing demand for improved accuracy and robustness in this classification task. However, due to weather conditions, time, lighting variations, and annotation costs, traditional deep learning methods still have limitations in extracting complex traffic scene features and achieving higher recognition accuracy. The previous classification methods for traffic scene images had gaps in multi-scale feature extraction and the combination of frequency domain, spatial, and channel attention. To address these issues, this paper proposes a multi-scale and multi-attention model based on Res2Net. Our proposed framework introduces an Adaptive Feature Refinement Pyramid Module (AFRPM) to enhance multi-scale feature extraction, thus improving the accuracy of traffic scene image classification. Additionally, we integrate frequency domain and spatial-channel attention mechanisms to develop recognition capabilities for complex backgrounds, objects of different scales, and local details in traffic scene images. The paper conducts the task of classifying traffic scene images using the Traffic-Net dataset. The experimental results demonstrate that our model achieves an accuracy of 96.88% on this dataset, which is an improvement of approximately 2% compared to the baseline Res2Net network. Furthermore, we validate the effectiveness of the proposed modules through ablation experiments.

microRNA-125b-1-3p mediates autophagy via the RRAGD/mTOR/ULK1 signaling pathway and mitigates atherosclerosis progression.

Atherosclerosis is characterised by lipid accumulation and formation of foam cells in arterial walls. Dysregulated autophagy is a crucial factor in atherosclerosis development. The significance of microRNA (miR)-125b-1-3p in cardiovascular disease is well-established; however, its precise role in regulating autophagy and impact on atherosclerosis in vascular smooth muscle cells (VSMCs) remain unclear. Here, we observed reduced autophagic activity and decreased miR-125b expression during atherosclerosis progression. miR-125b-1-3p overexpression significantly reduced atherosclerotic plaque development in mice; it also led to decreased lipid uptake and deposition in VSMCs, enhanced autophagy, and suppression of smooth muscle cell phenotypic changes in-vitro. An interaction between miR-125b-1-3p and the RRAGD/mTOR/ULK1 pathway was revealed, elucidating its role in promoting autophagy. Therefore, miR-125b-1-3p plays a pivotal role in enhancing autophagic processes, inhibiting foam cell formation in VSMCs and mitigating atherosclerosis progression, partly through RRAGD/mTOR/ULK1 signaling axis modulation. Thus, miR-125b-1-3p is a promising target for preventive and therapeutic strategies for atherosclerosis.

Exploring of Diverse Plant Communities and Adaptation to Drought Conditions Based on Advanced Logistics Model with Variable Growth.

Bio reciprocal symbiosis is very common in nature, such as soybeans providing food for rhizobia, which uses atmospheric nitrogen to synthesize nitrogen to provide nutrients to soybeans. This paper proposes an advanced Logistic model that adjusts to changes in precipitation and an environmental capacity parameter that varies with the level of symbiosis. The aim is to precisely depict the symbiotic relationship between plants and the interplay among symbiosis, competition, and independent growth of each population in the plant community, as precipitation changes by adapting finite difference method and tertiary Hermit interpolation. The model in this paper offers a comprehensive understanding of how plant populations interact with one another, providing valuable insights into the dynamics of plant growth and development. This paper finally finds that a combination of woody and herbaceous plants had the highest growth rate and total biomass, while herbaceous-only plants required 7 times longer to reach environmental capacity. This paper also reveals that irregular weather patterns, and different levels of species biomass can have different impacts on the recovery time of plant communities after drought or damage, and different types of pollution can have various effects on the community's regeneration, while the effect of overgrazing is the smallest.

Corrigendum: Seed coat pattern QTL and development in cowpea (Vigna unguiculata [L.] Walp.).

[This corrects the article DOI: 10.3389/fpls.2019.01346.].

Prevalence and risk factors for depression and anxiety in patients with nasolacrimal duct obstruction.

Objective: To investigate the prevalence and risk factors for depression and anxiety in patients with nasolacrimal duct obstruction (NLDO). Methods: We conducted a telephone-based survey of patients with NLDO who underwent dacryocystorhinostomy (DCR) at the Department of Ophthalmology of Peking University Third Hospital in China between January 2016 and January 2021. Depression and anxiety were assessed with the PHQ-9 (range 0-25) and STAI (range 20-80) scales. PHQ-9 ≥ 5 and STAI ≥ 55 were considered clinically significant. Logistic regression and linear regression were performed to determine the factors related to depression and anxiety. Results: Of 565 patients approached, 344 (60.9%) completed the survey. A total of 13.1% of patients had mild-severe depression and 63.4% had severe anxiety. Univariate logistic regression revealed that hypertension, dry eye, and cataract were associated with mild to severe depression (P = 0.018, 0.045, 0.035, respectively). Dry eye was associated with severe anxiety (P = 0.007). Univariate linear regression revealed that male and income levels were significantly negatively correlated with PHQ-9 scores (P = 0.011, 0.010, respectively). Hypertension and dry eye were significantly positively correlated with PHQ-9 scores (P = 0.030, P < 0.001, respectively). Male, income levels, and educational levels were significantly negatively correlated with STAI scores (P = 0.022, P < 0.001, P = 0.005, respectively). Dry eye was significantly positively correlated with STAI scores (P < 0.001). Conclusion: Prevalence of depression and anxiety disorders was relatively high among NLDO patients. Our results demonstrate the importance of depression and anxiety screening and psychosocial support for patients with NLDO, which can improve their quality of life and compliance with medical appointments.

Panscleritis After Blunt Ocular Trauma in A Child with Epididymitis.

We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground. Etiologic diagnosis played a key role in this case. Systemic examinations ruled out systemic autoimmune diseases, tumors, and infections as the cause of scleritis and suggested that the disease was caused by a local delayed-type hypersensitivity (DTH) induced by ocular trauma and was non-infectious. Still, the right epididymitis was infectious. Both conditions were treated successfully using steroids and antibiotics, respectively. Thus, early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.

Effect of Solution pH on the Biomechanics of Intact Cornea From Inflation Tests.

PURPOSE: To investigate the effect of different pH phosphate buffer solution (PBS) drops on intact corneal biomechanics. METHODS: Intact rabbit cornea with a 3 mm scleral skirt was sampled and immediately applied in inflation tests within 5 min. After preconditioning, a stable loading cycle from 0.3 to 6 kPa was performed followed by a 10 min interval. During the interval, the samples were randomized into four groups, with one control group receiving no drops and three groups with PBS drops of pH 6.9, 7.4 or 7.9 administration on the surface once per minute. The pressure and displacement were collected at the baseline and 10, 20 and 30 min following the administration. RESULTS: Continuous corneal thickness increase was manifested following the administration of PBS but not in the control group. There was significant swelling-independent corneal modulus reduction after PBS administration, which occurred mainly in the first 10 min. PBS of pH 6.9 achieved significantly smaller modulus reduction than that with pH 7.4 PBS adjusted for thickness changes (p < 0.05). Pressure-modulus curve linear fitting demonstrated that the curve coefficient significantly reduced following PBS administration, and the coefficient decline was smallest with pH 6.9 PBS among three PBS administration groups (p < 0.05). CONCLUSIONS: The study demonstrated that the PBS drops of various pH administration could decrease the corneal stiffness independent of corneal swelling. Following the PBS administration, the stiffness changes were more prominent as the posterior pressure increased, and the minimal effect was achieved with slightly acidic PBS. The research provides the essence for stabilizing the corneal biomechanical properties by regulating the pH value of tear film and intraocular pressure.

The impact of different corneal refractive surgeries on binocular dynamic visual acuity.

Purpose: To investigate the influence of different corneal refractive surgeries on dynamic visual acuity (DVA), and explore its potential influence factors. Methods: This was a prospective non-randomized study. Adult myopic patients undergoing bilateral laser-assisted sub-epithelial keratomileusis (LASEK), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), or small incision lenticule extraction (SMILE) with Plano refraction target were enrolled. Uncorrected and corrected distance visual acuity (UDVA/CDVA), manifest refraction and binocular optotype-moving DVA of 40 and 80 degrees per second (dps) were evaluated pre-operatively and post-operatively up to 3 months. Results: The study included 264 eyes of 132 subjects, with an average age of 27.0 ± 6.7 years, and females accounted for 59% of the participants. Significant improvement was observed at the 3-month visit for 40 dps (SMILE, P = 0.001; LASEK, P = 0.006; FS-LASIK, P = 0.010) and 80 dps (SMILE, P = 0.011; LASEK, P = 0.025; FS-LASIK, P = 0.012) DVA. Adjusting for pre-operative DVA, there was no significant difference in DVA among groups at 3 months post-operatively (P > 0.05 for multiple comparisons). Overall, multiple linear models demonstrated that post-operative DVA at 3 months was correlated with pre-operative DVA (40 dps, ß = 0.349, P = 0.001; 80 dps, ß = 0.447, P < 0.001), pre-operative spherical equivalent (40 dps, ß = 0.311, P = 0.003; 80 dps, ß = 0.261, P = 0.009) and post-operative UDVA (40 dps, ß = -0.224, P = 0.024; 80 dps, ß = -0.188, P = 0.05). Conclusion: Dynamic visual acuity at 3 months post-operatively of the three corneal refractive surgeries was better than that before the surgery in adult myopic patients, and there was no significant difference among different surgical techniques. Post-operative DVA at 3 months was found correlated with pre-operative DVA, pre-operative SE, and post-operative UDVA. With further improvement, DVA could be a promising functional visual indicator for myopic patients undergoing refractive surgeries.

Dynamic Visual Acuity After Small Incision Lenticule Extraction for Myopia Patients.

In the present study we compared dynamic visual acuity (DVA) of 84 eyes (for 42 adults with myopia; M age = 28.4, SD = 6.6 years; males = 38.1%, females = 61.9%) at 40 and 80 degree per second (dps) before surgery with eyeglass corrections and after a surgical procedure - a small incision lenticule extraction (SMILE). Participants underwent binocular SMILE surgery with plano refraction targets. Their eyeglass-corrected binocular DVA at 40 and 80 dps was evaluated preoperatively, and their uncorrected binocular DVA was assessed post-operatively at 1 week, 1 month and 3 months. The mean logMAR (logarithm of the minimum angle of resolution) uncorrected and corrected distance visual acuities (UDVA and CDVA) were -0.09 and -0.11 respectively, 3 months postoperatively. The mean preoperative eyeglass-corrected DVAs at 40 and 80 dps were 0.141 and 0.184, respectively, and significant improvements were observed for 40 dps and 80 dps DVAs 3 months postoperatively. Pearson's correlations were statistically significant between the postoperative DVAs at 3 months and for both the preoperative DVA and postoperative UDVA at both 40 dps and 80 dps. The change in the DVAs at 3 months were significantly associated with the preoperative DVAs at 40 dps and 80 dps. In conclusion, myopic patients' DVAs significantly improved following SMILE in comparison to corrected preoperative visual acuity when wearing eyeglasses. The post-SMILE DVA was associated with both the preoperative DVA and the postoperative UDVA.

Plantamajoside attenuates cardiac fibrosis via inhibiting AGEs activated-RAGE/autophagy/EndMT pathway.

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

The impact of COVID-19 home confinement on axial length in myopic children undergoing orthokeratology.

CLINICAL RELEVANCE: Understanding the impact of home confinement on axial length in myopic children undergoing orthokeratology (OK) treatment facilitates the management of myopia control during coronavirus disease 2019 (COVID-19) lockdown. BACKGROUND: The outbreak of COVID-19 and the corresponding home confinement measures have brought a considerable challenge to myopia control. The study aimed to investigate the influence of home quarantine on axial length in myopic children with OK treatment. METHODS: Axial length measurements during and before COVID-19 home confinement were retrospectively collected from the myopic children treated with OK, and the children were prospectively followed up after finishing the quarantine. The monthly axial length growth before, during and after confinement was calculated and compared in the full dataset and subgroups stratified by age. Influencing factors for monthly axial length growth during confinement were analysed. RESULTS: Ninety-two myopic children with OK treatment were enrolled in this study. In the full dataset, covariates adjusted (gender, time interval, baseline axial length and age) monthly axial length growth during confinement was not significantly different from that before (P = 0.213) or after the home confinement (P = 1.000). Multiple linear regression showed that the monthly axial length growth during confinement was negatively correlated with age (P = 0.002). Subgroup analysis based on age demonstrated that the adjusted monthly axial length growth was not significantly different among three periods (P > 0.05) for younger children. For children older than 12-year-old, the adjusted monthly axial length growth during home confinement was significantly slower than before the confinement (P = 0.011), but not the monthly axial length growth after the confinement (P = 1.000). CONCLUSIONS: COVID-19 home confinement does not increase the myopic axial length elongation in children with OK treatment.

Conjunctival sac bacterial culture of patients using levofloxacin eye drops before cataract surgery: a real-world, retrospective study.

BACKGROUND: The use of antibiotics preoperatively is effective to decrease the incidence of ocular bacterial infections but may lead to high resistance rate, especially on patients with multi-risk clinical factors. This study systematically analyzed real-world data (RWD) of patients to reveal the association between clinical factors and conjunctival sac bacterial load and offer prophylaxis suggestions. METHODS: We retrieved RWD of patients using levofloxacin eye drops (5 mL: 24.4 mg, 4 times a day for 3 days) preoperatively. Retrieved data included information on the conjunctival sac bacterial culture, sex, presence of hypertension and diabetes mellitus (DM), and history of hospital-based surgeries. Data was analyzed using SPSS 24.0. RESULTS: RWD of 15,415 cases (patients) were retrieved. Among these patients, 5,866 (38.1%) were males and 9,549 (61.9%) females. 5,960 (38.7%) patients had a history of hypertension, and 3,493 (22.7%) patients had a history of DM. 7,555 (49.0%) patients had a history of hospital-based operations. There were 274 (1.8%) positive bacterial cultures. Male patients with hypertension and DM may be at increased risk of having positive bacterial cultures (P < 0.05). Staphylococcus epidermidis (n = 56, 20.4%), Kocuria rosea (n = 37, 13.5%), and Micrococcus luteus (n = 32, 11.7%) were the top 3 isolated strains. Most bacterial strains were resistant to various antibiotics except rifampin, and 82.5% (33 of 40 isolates) of Staphylococcus epidermidis isolates had multidrug antibiotic resistance. Numbers of culture-positive Staphylococcus epidermidis isolates in the male group and non-DM group were greater than those in the female and DM groups, respectively. Micrococcus luteus (n = 11, 8.8%) was found less frequently in non-hypertension group than in hypertension group. CONCLUSION: Sex (Male) and the presence of hypertension and DM are risk factors for greater conjunctival sac bacterial loads. We offer a prophylactic suggestion based on the combined use of levofloxacin and rifampin. However, this approach may aggravate risk of multidrug resistance.

Binocular Dynamic Visual Acuity in Eyeglass-corrected Myopic Patients.

Current clinical visual assessment mainly focuses on static vision. However, static vision may not sufficiently reflect real-life visual function as moving optotypes are frequently observed daily. Dynamic visual acuity (DVA) might reflect real-life situations better, especially when objects are moving at high speeds. Myopia impacts static uncorrected distance visual acuity, conveniently corrected with eyeglasses. However, due to peripheral defocus and prism effects, eyeglass correction might affect DVA. The present research demonstrates a standard method to examine eyeglass-corrected DVA in myopia patients, and aimed to explore the influence of eyeglass correction on DVA. Initially, standard subjective refraction was performed to provide the eyeglass prescription to correct the refractive error. Then, binocular distance vision-corrected DVA was examined using the object-moving DVA protocol. Software was designed to display the moving optotypes according to the preset velocity and size on a screen. The optotype was the standard logarithmic visual chart letter E and moves from the middle of the left to the right side horizontally during the test. Moving optotypes with randomized opening direction for each size are displayed. The subjects were required to identify the opening direction of the optotype, and the DVA is defined as the minimum optotype that subjects could recognize, calculated according to the algorithm of logarithmic visual acuity. Then, the method was applied in 181 young myopic subjects with eyeglass-corrected-to-normal static visual acuity. Dominant eye, cycloplegic subjective refraction (sphere and cylinder), accommodation function (negative and positive relative accommodation, binocular cross-cylinder), and binocular DVA at 40 and 80 degrees per second (dps) were examined. The results showed that with increasing age, DVA first increased and then decreased. When myopia was fully corrected with eyeglasses, a worse binocular DVA was associated with more significant myopic refractive error. There was no correlation between the dominant eye, accommodation function, and binocular DVA.

Developing dynamic defocus curve for evaluating dynamic vision accommodative function.

BACKGROUND: To assess dynamic visual acuity (DVA) under different defocus statuses and explore the assessment of dynamic vision accommodation. METHODS: Twenty subjects (6 males and 14 females) aged 18 to 35 were recruited. Nonmydriatic subjective refraction (sphere and cylinder) and accommodative tests including negative relative accommodation (NRA), positive relative accommodation (PRA), binocular cross cylinder (BCC) and accommodative facility using a flipper were performed. Binocular static visual acuity (SVA) and DVA at 40 degrees per second (dps) were measured under different defocus statuses (+1.5D to -4D in -0.5D steps) based on the refractive error fully corrected. Static and dynamic defocus curves were plotted. The area under the curve (AUC) and corrected dynamic vision accommodation (CDVAc) were calculated. RESULTS: The study showed that the dynamic defocus curve fitted the cubic curve properly (p<0.001). DVA was significantly worse than SVA at all defocused statuses (p<0.001), and the difference was more significant at greater defocus diopters. Single factor analysis indicated that CDVAc was significantly correlated with NRA-PRA (p=0.012) and AUCdynamic (p<0.001). Significant associations were observed between AUCdynamic and PRA (p=0.013) as well as NRA-PRA (p=0.021). Meanwhile, DVA was positively correlated with PRA at 0D, -1.0D, -1.5D, -2.5D and -3.0D (p<0.05) and with NRA-PRA at 0D, -1.0D, -1.5D, -2.0D and -2.5D (p<0.05). Multiple factor regression analysis indicated that CDVAc (0D ~ -3.5D) and SVA (+1.5D ~ +1.0D & -2.5D ~ -4.0D) were significant influential factors for defocused DVA (p<0.05). CONCLUSIONS: Our study demonstrated that DVA had a defocus curve similar to that of SVA. CDVAc was feasible for the assessment of dynamic vision accommodative function. The dynamic defocus curve test could efficiently be applied in the evaluation of dynamic visual performance under different defocus statuses.

Three-dimensional topographic changes of anterior chamber depth following phacoemulsification with intraocular lens implantation in cataract patients.

PURPOSE: To investigate the three-dimensional topographic changes of anterior chamber depth (ACD) following cataract surgery. METHODS: Seventy-eight eyes with age-related cataract undergoing phacoemulsification and intraocular lens (IOL) implantation were retrospectively enrolled. Participants were evaluated with Pentacam for ACD topography before and approximately four weeks after the surgery. The absolute changes of ACD (AACD) and the relative changes of ACD (RACD) topography were calculated, and three-dimensional topographic contours were plotted. The influence of age, gender, distance to corneal apex (DCA), temporal-nasal and superior-inferior on AACD and RACD was analyzed. RESULTS: Both AACD and RACD were negatively correlated with the DCA (p < 0.001; p < 0.001) and positively correlated with the age at all DCA (p < 0.05 for all the analyses). Significantly greater AACD and RACD were observed in female subjects (p < 0.05, respectively, at all DCA). AACD was significantly larger in the temporal compared with the nasal region (p < 0.001) and at the superior compared with the inferior region (p < 0.001), but not RACD. Subgroup analysis indicated that the significant difference of the AACD between the temporal and nasal regions was manifested at the DCA of more than 6 mm (p < 0.001), and the difference between the superior and inferior regions was observed at 2 mm DCA for both AACD (p < 0.001) and RACD (p = 0.001). CONCLUSIONS: We depicted the topographic changes of ACD following cataract surgery and found that it was significantly influenced by age, gender, DCA and quadrant location. The research provided the basis for including postoperative ACD topography prediction before cataract surgery in the future.

Prevalence and Risk Factors of Dry Eye Symptoms after Successful Dacryocystorhinostomy for Patients with Lacrimal Passage Obstruction.

PURPOSE: To investigate the prevalence of dry eye symptoms after successful dacryocystorhinostomy and explore the potential risk factors. METHODS: This cross-sectional study included 565 patients with lacrimal passage obstruction (LPO) who underwent external dacryocystorhinostomy. Ocular Surface Disease Index (OSDI) total score of 13 or more was regarded as presence of dry eye symptoms. OSDI total score greater than 22 combined with self-reported dry eye was defined as symptomatic dry eye. Logistic regression and linear regression were used to examine the associations between OSDI scores and its potentially predictive factors. RESULTS: Of the 565 patients, 344 completed the questionnaire, among which 101(29.4%) patients presented with dry eye symptoms, including 53(15.4%) mild, 14(4.1%) moderate and 34(9.9%) severe, and 48(14.0%) patients can be defined as symptomatic dry eye. Univariate logistic regression revealed that age, educational levels, income levels, and hypertension were significantly correlated with the presence of dry eye symptoms (P < 0.05). After multivariate adjustment, lower income levels were found significantly associated with dry eye symptoms (P < 0.05). Univariate linear regression demonstrated that age, lower educational levels, surgery history, and hypertension were significantly associated with OSDI total score (P = 0.037, 0.012, 0.022, 0.029 respectively). Multivariate stepwise linear regression manifested that educational levels and the surgery history influenced the OSDI total score mostly (P = 0.021, 0.036 respectively). CONCLUSIONS: Dry eye problem of LPO patients after successful dacryocystorhinostomy cannot be ignored. In the preoperative evaluation, we should pay special attention to the elderly patients with lower educational levels, lower income levels or systemic diseases.

Anti-Inflammatory Effect of Dimethyl Fumarate Associates with the Inhibition of Thioredoxin Reductase 1 in RAW 264.7 Cells.

Macrophages secrete a variety of pro-inflammatory cytokines in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) but abnormal release of cytokines unfortunately promotes cytokine storms. Dimethyl fumarate (DMF), an FDA-approved drug for multiple sclerosis (MS) treatment, has been found as an effective therapeutic agent for resolution. In this study, the anti-inflammatory effect of DMF was found to correlate to selenoprotein thioredoxin reductase 1 (TXNRD1). DMF irreversibly modified the Sec498 residue and C-terminal catalytic cysteine residues of TXNRD1 in a time- and dose-dependent manner. In LPS-stimulated RAW 264.7 cells, cellular TXNRD activity was increased through up-regulation of the protein level and DMF inhibited TXNRD activity and the nitric oxide (NO) production of RAW 264.7 cells. Meanwhile, the inhibition of TXNRD1 by DMF would contribute to the redox regulation of inflammation and promote the nuclear factor erythroid 2-related factor 2 (NRF2) activation. Notably, inhibition of cellular TXNRD1 by auranofin or TRi-1 showed anti-inflammatory effect in RAW 264.7 cells. This finding demonstrated that targeting TXNRD1 is a potential mechanism of using immunometabolites for dousing inflammation in response to pathogens and highlights the potential of TXNRD1 inhibitors in immune regulation.

MiR-181c sensitizes ovarian cancer cells to paclitaxel by targeting GRP78 through the PI3K/Akt pathway.

Primary cytoreductive surgery with platinum-taxane-based chemotherapy is the standard treatment for ovarian cancer (OC) patients; however, resistance to chemotherapy is a contributing factor to OC mortality. Paclitaxel (PTX), the most widely used taxane, has become the first-line drug against OC. The molecular mechanism of PTX resistance is different from that of platinum-based agents and is still not completely elucidated. Our previous study showed that glucose-regulated protein 78 (GRP78) is involved in the resistance of OC cells to PTX. However, little is known regarding endogenous inhibitors of this gene. MicroRNAs (miRNAs) play critical roles in the regulation of gene expression; therefore, we sought to identify miRNA(s) with potential to target GRP78 under the hypothesis that miRNA(s) could serve as potential therapeutic targets. Here, we show that miR-181c, predicted to target GRP78, was downregulated in PTX-resistant OC cells and tissues. MiR-181c downregulated GRP78 expression and induced apoptosis by directly targeting its 3'-untranslated region (UTR). Overexpression of miR-181c sensitized resistant OC to PTX by inhibiting the PI3K/Akt pathway in vitro and in vivo. Taken together, our findings indicate that the delivery of miR-181c can efficiently suppress GRP78 expression and GRP78-mediated PTX resistance in OC and suggest that this strategy has therapeutic potential.

Xinyang Tablet inhibits MLK3-mediated pyroptosis to attenuate inflammation and cardiac dysfunction in pressure overload.

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been traditionally used in the treatment of cardiovascular diseases (CVDs). Our previous study indicated that XYT exhibited protective effects in heart failure (HF). AIM OF THE STUDY: The aim of the present study was to determine the protective effects of XYT in pressure overload induced HF and to elucidate its underlying mechanisms of action. MATERIALS AND METHODS: We analyzed XYT content using high-performance liquid chromatography (HPLC.). Mice were subjected to transverse aortic constriction (TAC) to generate pressure overload-induced cardiac remodeling and were then orally administered XYT or URMC-099 for 1 week after the operation. HL1 mouse cardiomyoblasts were induced by lipopolysaccharides (LPS) to trigger pyroptosis and were then treated with XYT or URMC-099. We used echocardiography (ECG), hematoxylin and eosin (H&E) staining, Masson's trichrome staining and a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay to evaluate the effects of XYT. Messenger ribonucleic acid (mRNA) levels of collagen metabolism biomarkers and inflammation-related factors were detected. We determined protein levels of inflammation- and pyroptosis-related signaling pathway members via Western blot (WB). Caspase-1 activity was measured in cell lysate using a Caspase-1 Activity Assay Kit. Subsequently, to define the candidate ingredients in XYT that regulate mixed-lineage kinase-3 (MLK3), we used molecular docking (MD) to predict and evaluate binding affinity with MLK3. Finally, we screened 24 active potential compounds that regulate MLK3 via MD. RESULTS: ECG, H&E staining, Masson's trichrome staining and TUNEL assay results showed that XYT remarkably improved heart function, amelorated myocardial fibrosis and inhibited apoptosis in vivo. Moreover, it reduced expression of proteins or mRNAs related to collagen metabolism, including collagen type 1 (COL1), fibronectin (FN), alpha smooth-muscle actin (α-SMA), and matrix metalloproteinases-2 and -9 (MMP-2, MMP-9). XYT also inhibited inflammation and the induction of pyroptosis at an early stage, as well as attenuated inflammation and pyroptosis levels in vitro. CONCLUSION: Our data indicated that XYT exerted protective effects against pressure overload induced myocardial fibrosis (MF), which might be associated with the induction of pyroptosis-mediated MLK3 signaling.