Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against non-alcoholic fatty liver disease.

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on NAFLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on NAFLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of NAFLD. In addition, this study revealed that in addition to the canonical TGF-ß/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in NAFLD progression. Conclusions: Ursolic acid could improve immune inflammation in NAFLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Causal effects of gut microbiome on autoimmune liver disease: a two-sample Mendelian randomization study.

BACKGROUND: Epidemiological studies have indicated a potential link between the gut microbiome and autoimmune liver disease (AILD) such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The relationship between the gut microbiome and autoimmune liver disease is still uncertain due to confounding variables. In our study, we aim to shed light on this relationship by employing a two-sample Mendelian randomization approach. METHODS: We conducted a two-sample Mendelian randomization (MR) study using the R package "TwoSampleMR". The exposure data consisted of genetic variants associated with 194 bacterial traits obtained from the MiBioGen consortium. Summary statistics for AILD were obtained from the GWAS Catalog website. Furthermore, a series of sensitivity analyses were performed to validate the initial MR results. RESULTS: There were two, four and three bacteria traits associated with an increased risk of AIH. PBC, and PSC respectively. In contrast, there were five, two and five bacteria traits associated with a decreased risk for AIH, PBC and PSC. Notably, the genus_Clostridium_innocuum_group showed a negative association with AIH (OR = 0.67, 95% CI: 0.49-0.93), and the genus_Actinomyces was found to be genetically associated with a decreased risk of PSC (OR = 0.62, 95% CI: 0.42-0.90). CONCLUSIONS: Our study identified the causal impact of specific bacterial features on the risk of AILD subtypes. Particularly, the genus_Clostridium_innocuum_group and the genus_Actinomyces demonstrated significant protective effects against AIH and PSC respectively. These findings provide further support for the potential use of targeted probiotics in the management of AILD.

Aqueous-Based Inorganic Colloidal Halide Perovskites Customizing Liquid Scintillators.

Compared to solid scintillators and organic liquid scintillators, aqueous-based liquid scintillators (AbLS) have more superiority in highly flexible scalability, yet are now limited by their low light yield (≈100 photons MeV-1 ). Here, aqueous-based inorganic colloidal halide perovskites with high photoluminescence quantum yield (PLQY) of three primary color luminescence up to 88.1% (red), 96% (green), and 81.8% (blue) are respectively synthesized, and a new generation of colloidal perovskite-mediated AbLS (PAbLS) with light yield increased in comparison with the commercial scintillator AbLS is fabricated. This paper exhibits that the excellent PLQY and colloidal dispersion of halide perovskites benefit from poly(ethylene glycol) modification and this modification ensures the vacancy inhibition and formation of defect-free surfaces in an aqueous solution. Moreover, their high luminescent emission can be maintained for 100 days at low temperatures, and such modification also promises the heat-to-cold customization of operating temperature even in ice below 0 °C. Finally, depending on the light yield of around 3058 and 8037 photons MeV-1 at room temperature and low temperature, PAbLS with shape/size scalability exhibit their robust radiation hardness (dose rate as high as 23 mGy s-1 ) and conceptual application potential in high-energy ray radiation detection from every angle of 360°.

Highly Ambient Stable CsSnBr3 Perovskite via a New Facile Room-Temperature "Coprecipitation" Strategy.

Tin-based perovskites are becoming promising alternatives to lead-based perovskites with eco-friendly merit and tantalizing photophysical properties. Unfortunately, the lack of facile, low-cost synthesis approaches associated with extremely poor stability greatly restrict their practical applications. Herein, a facile room-temperature "coprecipitation" method utilizing ethanol (EtOH) solvent and salicylic acid (SA) additive is proposed for synthesizing highly stable cubic phase CsSnBr3 perovskite. Experimental results show that ethanol solvent and SA additive can not only effectively prevent the oxidation of Sn2+ during the synthesis processes but also stabilize the as-synthesized CsSnBr3 perovskite. These are mainly ascribed to the protection effect of ethanol and SA, which are attached on the surface of CsSnBr3 perovskite by coordinating with Br- and Sn2+ ions, respectively. As a result, CsSnBr3 perovskite can be obtained in open air and exhibits exceptional oxygen resistibility under moist air conditions (temperature: 24.2-25.8 °C; relative humidity: 63-78%). Absorption remains unchanged and photoluminescence (PL) intensity is vastly maintained (∼69%) after storage for 10 days, better than bulk CsSnBr3 perovskite film synthesized by spin-coating method whose PL intensity is decreased to 43% after storage for 12 h. This work represents a step toward stable tin-based perovskite by a facile and low-cost strategy.

Protein engineering, cofactor engineering, and surface display engineering to achieve whole-cell catalytic production of chondroitin sulfate A.

Chondroitin sulfate A (CSA) is a valuable glycosaminoglycan that has great market demand. However, current synthetic methods are limited by requiring the expensive sulfate group donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) and inefficient enzyme carbohydrate sulfotransferase 11 (CHST11). Herein, we report the design and integration of the PAPS synthesis and sulfotransferase pathways to realize whole-cell catalytic production of CSA. Using mechanism-based protein engineering, we improved the thermostability and catalytic efficiency of CHST11; its Tm and half-life increased by 6.9°C and 3.5 h, respectively, and its specific activity increased 2.1-fold. Via cofactor engineering, we designed a dual-cycle strategy of regenerating ATP and PAPS to increase the supply of PAPS. Through surface display engineering, we realized the outer membrane expression of CHST11 and constructed a whole-cell catalytic system of CSA production with an 89.5% conversion rate. This whole-cell catalytic process provides a promising method for the industrial production of CSA.

A nomogram model for predicting ocular GVHD following allo-HSCT based on risk factors.

OBJECTIVE: To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). METHODS: This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. RESULTS: Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895-1.000) and 0.969 (95% CI, 0.846-1.000), respectively.And the Hosmer-Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). CONCLUSION: We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.

Embryonic stem cell extracellular vesicles reverse the senescence of retinal pigment epithelial cells by the p38MAPK pathway.

Retinal pigment epithelial (RPE) cellular senescence is regarded as an initiator for age-related macular degeneration (AMD). We previously demonstrated that by the coculture way, embryonic stem cells (ESCs) can reverse the senescence of RPE cells, but xenograft cells can cause a plethora of adverse effects. Extracellular vesicles (EVs) derived from ESCs can act as messengers to mediate nearby cell activities and have the same potential as ESCs to reverse RPE senescence. Furthermore, ESC-EVs have achieved preliminary efficacy while treating many age-related diseases. The present study aimed to test the effect of ESC-EVs on the replicative senescence model of RPE cells as well as its mechanism. The results showed that ESC-EVs enhanced the proliferative ability and cell cycle transition of senescent RPE cells, whereas reduced the senescence-associated galactosidase (SA-ß-gal) staining rate, as well as the levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Moreover, classical markers of cellular senescence p21WAF1/CIP1 (p21) and p16INK4a (p16) were downregulated. The bioinformatic analysis and further study showed that the inhibition of the p38MAPK pathway by ESC-EVs played a pivotal role in RPE cellular senescence-reversing effect, which was ameliorated or even abolished when dehydrocorydaline were administrated simultaneously, demonstrating that ESC-EVs can effectively reverse RPE cellular senesence by inhibiting the p38MAPK pathway, thus highlights the potential of ESC-derived EVs as biomaterials for preventative and protective therapy in AMD.

Tear film cytokines as prognostic indicators for predicting early recurrent pterygium.

Cytokine profiles in tears have become a noninvasive biomarker for various ocular surface diseases. Therefore, the preoperative profile of cytokines in tear samples of 89 primary pterygium patients were obtained from Zhongshan Ophthalmic Center during 2015-2017. Compared to the tear cytokines in primary groups, the concentrations of IL-8, MMP-1, MMP-9, bFGF and VEGF were generally higher in recurrent pterygium group. The five cytokines were used to build diagnostic models by multiple machine learning algorithms, which can accurately distinguish non-recurrent and recurrent samples of primary pterygium patients. Besides, these cytokines were significantly associated with Recurrent-free survival (RFS) time in pterygium patients and further applied to develop a prognostic model which can estimate the prognosis of pterygium after resection. Afterward, a novel nomogram combined risk score of cytokines related biomarker and clinical characteristics was constructed, which manifested ideal accuracies to predict the 1 and 2 years' probability of pterygium recurrent events. Thus, our finding provides a more simple and accurate prediction for early pterygium recurrence after resection. It also affords a useful tool for ophthalmologists to choose the optimal treatment strategies for pterygium patients.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS OF MICROVASCULAR AND NEURAL CHANGES IN PRIMARY PULMONARY HYPERTENSION.

PURPOSE: To investigate the microvascular and neural changes in primary pulmonary hypertension (PPH) patients compared with healthy controls. METHODS: Forty-four eyes of 22 PPH patients were included in this observational clinical cohort study, and 44 eyes of 22 healthy participants were enrolled as controls. Optical coherence tomography angiography images were obtained from each participant using the RTVue XR Avanti device with AngioVue software 2.0. RESULTS: Regarding the total macular-associated vessel density, including that of the superficial and deep retina, the optic disk-associated capillary density, including that of the whole image, capillary density inside the disk, and the peripapillary region, was significantly lower in the PPH group than in the control group. There was a similar trend in the retinal nerve fiber layer thickness and the ganglion cell complex thickness, whereas the focal loss volume and the global loss volume were greater in the PPH group than the control group. CONCLUSION: Changes in the capillary density and thickness of the retina and the optic nerve head in PPH patients can be detected by optical coherence tomography angiography. Parameters including the macular-associated vessel density, optic disk-associated capillary density, retinal nerve fiber layer, ganglion cell complex, focal loss volume, and global loss volume may provide useful evidence for the early detection of microvascular and neural impairments in patients with PPH.

Which treatment is best for patients with AJCC stage IV bladder cancer?

PURPOSE: We sought to identify the method that could obtain the best survival rate for AJCC stage IV bladder cancer (BCa) patients. METHODS: Patients with AJCC stage IV BCa diagnosed between 2004 and 2015 were identified using the Surveillance, epidemiology and end results (SEER) database. Kaplan-Meier curves and log-rank test were used for overall survival (OS) and cancer-specific survival (CSS). Multivariable Cox regression was used to determine factors associated with all-cause mortality (ACM) and cancer-specific mortality (CSM). RESULTS: We found that among the 11824 patients, the number of patients who received chemotherapy (CT), radiotherapy (RT) and radical cystectomy (RC) was 6243 (52.8%), 2005 (17.0%) and 4987 (42.2%), respectively. Patients who received CT or RC had improved OS (26.4% vs. 11.7%, p < 0.001 and 27.3% vs. 13.7%, p < 0.001, respectively), but patients who underwent RT alone had lower OS (14.4% vs. 20.5%, p < 0.001). Furthermore, CT combined with RC was associated with the lowest ACM (hazard ratio (HR) = 0.26, 95% CI 0.24-0.28, p < 0.001) and the lowest CSM (HR = 0.24, 95% CI 0.22-0.26, p < 0.001). Patients who only received RT had the highest ACM (HR = 0.84, 95% CI 0.77-0.92, p < 0.001) and the highest CSM (HR = 0.85, 95% CI 0.77-0.94, p = 0.002). CONCLUSIONS: We concluded that CT combined with RC was the best method with the highest survival rate for patients with AJCC stage IV BCa and that CT combined with RC had more benefits in improving OS and CSS than did RT alone.

Enhanced photoluminescence and energy transfer performance of Y3Al4GaO12:Mn4+,Dy3+ phosphors for plant growth LED lights.

Plant growth LEDs have attracted broad attention in modern society, desperate for specific phosphors with a characteristic emission band. A novel Mn4+ and Dy3+ co-doped Y3Al4GaO12 phosphor were successfully prepared through a conventional high-temperature solid-state reaction. A three band emission including red (625-700 nm), orange (550-607 nm) and blue (462-490 nm) is observed in these phosphors when excited under a near-UV lamp, which is ascribed to 2E → 4A2 of Mn4+, 4F9/2 → 6H15/2 and 4F9/2 → 6H13/2 of Dy3+, respectively. The three emissions match the absorption spectra of chlorophyll A and chlorophyll B well. Meanwhile, the energy transfer from Dy3+ to Mn4+ was confirmed by the luminescence spectra and lifetime analysis. Finally, an LED device was fabricated that consisted of a 365 nm ultraviolet chip and the Y3Al4GaO12:Mn4+,Dy3+ phosphor. The excellent properties indicate that the synthesized phosphor has a promising application in the optical agricultural industry.

Research on the static experiment of super heavy crude oil demulsification and dehydration using ultrasonic wave and audible sound wave at high temperatures.

In this paper, the static experiment of super heavy crude oil demulsification and dehydration using ultrasonic irradiation at high temperatures is carried out. How the all factors, such as ultrasonic frequency, sound intensity, ultrasonic power, ultrasonic treatment time, sedimentation time, temperature and water ratio, affect ultrasonic crude oil demulsification and dehydration are summarized though this experiment. In addition, recent progress on ultrasonic demulsification equipment in China are reviewed. The purpose of this paper is to provide equipment and technical support for the extensive application of the technique of ultrasonic demulsification and dehydration.