Farnesoid X receptor modulator 12ß-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid represses liver fibrosis by inhibiting ERK/p38 signaling pathways.

Liver fibrosis is a common pathological process in the progression of several chronic liver diseases to cirrhosis and hepatocellular carcinoma. Therefore, the development of medications that can repress the progress of liver fibrosis is essential. We discovered that initially, 12ß-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid (12d-OA), a farnesoid X receptor (FXR) modulator, possessed potential anti-fibrotic properties. Through an in-depth study, we revealed that 12d-OA not only inhibited the expression of fibrogenic markers in the LX-2 cells and HSC-T6 cells but also exhibited significant protective effects against liver injury and liver fibrosis in bile duct ligation (BDL) rats. Further exploration of its molecular mechanism indicated that 12d-OA exerted antifibrotic activity by inhibiting the extracellular signal-regulated kinase (ERK)/stress-activated protein kinase (p38) signaling pathways. Consequently, the great effects of 12d-OA in vitro and in vivo suggest that it may be a good candidate for liver fibrosis.

Research on the ditching resistance reduction of self-excited vibrations ditching device based on MBD-DEM coupling simulation.

In plant horticulture, furrow fertilizing is a common method to promote plant nutrient absorption and to effectively avoid fertilizer waste. Considering the high resistance caused by soil compaction in southern orchards, an energy-saving ditching device was proposed. A standard ditching blade with self-excited vibration device was designed, and operated in sandy clay with a tillage depth of 30cm. To conduct self-excited vibration ditching experiments, a simulation model of the interaction between soil and the ditching mechanism was established by coupling the ADAMS and EDEM software. To begin with, the ditching device model was first set up, taking into account its motion and morphological characteristics. Then, the MBD-DEM coupling method was employed to investigate the interaction mechanism and the effect of ditching between the soil particles and the ditching blade. Afterwards, the time-domain and frequency-domain characteristics of vibration signals during the ditching process were analyzed using the fast fourier transform (FFT) method, and the energy distribution characteristics were extracted using power spectral density (PSD). The experimental results revealed that the vibrations ditching device has reciprocating displacement in the Dx direction and torsional displacements in the θy and θz directions during operation, verifying the correctness of the coupling simulation and the effectiveness of vibrations ditching resistance reduction. Also, a load vibrations ditching bench test was conducted, and the results demonstrated that the self-excited vibrations ditching device, compared with common ditching device, achieved a reduction in ditching resistance of up to 12.3%. The reasonable parameters of spring stiffness, spring damping, and spring quality in self-excited vibrations ditching device can achieve a satisfied ditching performance with relatively low torque consumption at an appropriate speed.

Experimental and Theoretical Studies on the Shear Performance of Concrete Beams Reinforced with Fiber-Reinforced Polymer Stirrups.

In this paper, the shear behavior of concrete beams reinforced with FRP stirrups is studied. The shear performances of six concrete beams with a size of 150 mm × 300 mm × 3000 mm under four-point loading up to failure were experimentally analyzed. The critical parameters included the shear span to depth ratio (λ) and stirrup spacing (S). The test results revealed that as λ increased from 1 to 2, 3, and 4, the ultimate shear capacity of the beam decreases by 50.5%, 67.7%, and 69.2%, respectively. Meanwhile, as S increased from 100 mm to 150 mm and 200 mm, the ultimate shear capacity decreased by 16.1% and 44.6%, respectively. A new shear capacity calculation model of concrete beam reinforced with FRP stirrups was also proposed, which further considered the shear capacity of the FRP stirrups on the basis of the shear capacity of an RC beam without stirrups using the strut-and-tie model. Finally, the experiment and calculation results of 56 beam specimens reinforced with FRP stirrups extracted from this paper and previous studies were compared using the calculation models proposed in this paper, in order to evaluate the accuracy of these calculation models.

Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.

There exists a huge number of patients suffering from chronic liver disease worldwide. As a disease with high incidence and mortality worldwide, strengthening the research on the pathogenesis of chronic liver disease and the development of novel drugs is an important issue related to the health of all human beings. Phosphorylation modification of proteins plays a crucial role in cellular signal transduction, and phosphatases are involved in the development of liver diseases. Therefore, this article summarized the important role of protein phosphatases in chronic liver disease with the aim of facilitating the development of drugs targeting protein phosphatases for the treatment of chronic liver disease.

Enhanced Performance and High Resistance to Efficiency Degradation of Blue Quantum-Dot Light-Emitting Diodes Using the Lewis Base Blended Hole-Transporting Layers.

The distinctive characteristics of blue quantum dots (QDs) such as their deep valence band and large bandgap give rise to an elevated hole injection barrier between the hole transport layers (HTLs) and the QD active layer. This results in an imbalance of carrier transport and injection across the device, leading to a degrading performance in QD light-emitting diodes (QLEDs). In this paper, high-efficiency and low-efficiency degradation blue CdSe/CdS/ZnS QLEDs were fabricated by using the Lewis base, 1,2-bis(diphenylphosphino)ethane (DPPE), blended with poly(9-vinylcarbazole) (PVK) (DPPE:PVK) as HTLs. The device performance of blue QLEDs can be finely adjusted by manipulating the blending ratio between DPPE and PVK. When 4 wt % DPPE was blended with PVK (4 wt % DPPE:PVK) as the HTL, the device achieved its optimal performance. Compared to the device with neat PVK as the HTL, the turn-on voltage of blue QLEDs with the 4 wt % DPPE:PVK HTL is reduced from 3.21 to 2.9 V. The maximum current efficiency (CE) and external quantum efficiency (EQE) of blue QLEDs increase from 2.92 cd A-1 and 5.89% in neat PVK to 5.75 cd A-1 and 11.75% for the 4 wt % DPPE:PVK HTL. Furthermore, the QLEDs incorporating DPPE:PVK HTLs exhibited exceptional resistance to efficiency degradation (EQE = 8.83%@L = 12,000 cd m-2 for 4 wt % DPPE:PVK as the HTL and EQE = 2.80%@L = 12,000 cd m-2 for neat PVK as the HTL). A more in-depth analysis reveals that enhanced device performance results from the chelating and bridging effect of the bidentate ligand Lewis base DPPE. These effects strengthen the binding of free metal ions in the blue QDs, reduce the charge barriers, enhance the contact between the HTLs and the QD active layer, and ultimately improve hole injection.

Design, synthesis and triglyceride-lowering activity of tricyclic matrine derivatives for the intervention of non-alcoholic fatty liver disease.

Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Primary mechanism study revealed that upregulation of peroxisome proliferator-activated receptors α (PPARα)-carnitine palmitoyltransferase 1A (CPT1A) pathway mediated the efficacy of 7n. Our study provides powerful information for developing this kind of compound into a new class of anti-NAFLD candidates, and compound 7n is worthy of further investigation as an ideal lead compound.

LncRNA-HANR exacerbates malignant behaviors of cholangiocarcinoma cells through activating Notch pathway.

Objectives: Cholangiocarcinoma (CHOL) is a malignant tumor from extrahepatic bile duct with poor prognosis. The critical roles of long non-coding RNAs (lncRNAs) in cancers including CHOL have been unveiled in recent decades. The present study was aimed to investigate the role and mechanism of a certain lncRNA, namely, hepatocellular carcinoma (HCC) associated long non-coding RNA (HANR) in CHOL. Methods: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was applied for detecting gene expression. Functional assays were done for assessing CHOL cell malignancy and mechanistic assays were conducted for analyzing correlation between HANR and Notch signal pathway, as well as the relation between HANR and Notch intracellular domain (NICD) in CHOL cells. Results: HANR was detected to be significantly overexpressed in CHOL cell lines. HANR silence inhibited cell proliferation, migration and stemness. Besides, HANR could positively regulate the Notch signaling pathway through modulating RBP-JK. HANR could bind to NICD and affect the transcriptional activity of RBP-JK. Furthermore, p-Notch1-NICD-r could wholly countervail the inhibitory effects of HANR silence on CHOL cell proliferation, migration and stemness. Conclusion: HANR could activate Notch pathway by regulating the RBP-JK transcriptional activity, thus contributing to exacerbated malignant behaviors of CHOL cells.

[Mechanism of dexamethasone combined with glutamine in reducing lung inflammation and pulmonary edema in rats with acute lung injury].

Objective To investigate the effect of dexamethasone (DEX) combined with glutamine (Gln) on lung inflammation and pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS) and its related mechanisms. Methods Fifty Wistar rats were randomly divided into control group, model group, dexamethasone group (DEX) and DEX combined with Gln group. Except for the control group, rats in other groups were injected with 6 mg/kg LPS intraperitoneally to induce an acute lung injury. The mRNA expression of p38 MAPK, NLRP3, and NF-κB in lung tissue were detected by real-time quantitative PCR. The protein expressions of p-p38 MAPK, NLRP3, phosphorylated inhibitor of nuclear factor κB (p-IκB), NF-κB p65, aquaporin 1 (AQP1) and AQP5 in lung tissue were detected by Western blot analysis. ELISA was used to detect the content of serum tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß). Spectrophotometer was employed to detect the content of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in lung tissue. Results Compared with the control group, the lung index of the model group decreased, the content of the serum inflammatory factors TNF-α, IL-6 and IL-1ß significantly increased, and the protein expression of p38 MAPK, NLRP3, NF-κB mRNA, p-p38 MAPK, NLRP3, p-IκB and NF-κB p65 in the lung tissue significantly increased, while that of AQP1, AQP5 decreased, and the content of SOD and GSH-Px in lung tissue decreased, while that of MDA increased; Compared with the model group, the above mentioned symptoms and indicators in each treatment group were significantly improved, among which the DEX combined with Gln group was the most significant. Conclusion DEX combined with Gln can inhibit inflammation, resist oxidative damage, relieve pulmonary edema, and prevent acute lung injury. Its mechanism is related to inhibiting the activation of p38 MAPK, NLRP3, and NF-κB signaling pathways, promoting the expression of AQP1 and AQP5, and promoting the activity of antioxidant products.

Application of Retrospective Outcome Special Attention Nursing in the Continuous Nursing of Patients with Heart Failure During Vulnerable Period.

Objective: To assess the effectiveness and benefits of retrospective outcome special attention nursing in providing continuous care for patients with heart failure during a vulnerable period. Methods: 96 patients with heart failure discharged from the hospital between January 2021 and January 2022 were included in the study. Patients discharged from January 2021 to June 2021 (48 cases) formed the single group, while those from July 2021 to January 2022 (48 cases) constituted the combined group. The single group received standard continuous nursing, while the combined group underwent retrospective outcome special attention nursing intervention in addition to standard care. Following the interventions, cardiac function-related indicators, negative emotions, self-management ability, health behavior, quality of life, and readmission rates were compared between the two groups. Results: Following the intervention, the combined group exhibited significant improvements, including enhanced 6-minute walk test (6MWT) results (P < .05) and lower scores on the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) (P < .05), indicating reduced anxiety and depression levels. The combined group also demonstrated superior self-management abilities, with higher scores in health behavior dimensions (nutrition, exercise, health responsibility, stress coping) and a higher overall self-management score (P < .05). However, the combined group had lower quality of life scores (P < .05). Notably, the combined group's readmission rate was significantly lower at 14.58% (7/48), compared to 33.33% (16/48) in the single group (P < .05). Conclusion: Retrospective outcome special attention nursing improves cardiac function, emotional regulation, self-management, health behaviors, quality of life, and reduces readmission rates in heart failure patients during vulnerable periods.

Cation Defect-Engineered Boost Fast Kinetics of Two-Dimensional Topological Bi2 Se3 Cathode for High-Performance Aqueous Zn-Ion Batteries.

The challenge with aqueous zinc-ion batteries (ZIBs) lies in finding suitable cathode materials that can provide high capacity and fast kinetics. Herein, two-dimensional topological Bi2 Se3 with acceptable Bi-vacancies for ZIBs cathode (Cu-Bi2-x Se3 ) is constructed through one-step hydrothermal process accompanied by Cu heteroatom introduction. The cation-deficient Cu-Bi2-x Se3 nanosheets (≈4 nm) bring improved conductivity from large surface topological metal states contribution and enhanced bulk conductivity. Besides, the increased adsorption energy and reduced Zn2+ migration barrier demonstrated by density-functional theory (DFT) calculations illustrate the decreased Coulombic ion-lattice repulsion of Cu-Bi2-x Se3 . Therefore, Cu-Bi2-x Se3 exhibits both enhanced ion and electron transport capability, leading to more carrier reversible insertion proved by in situ synchrotron X-ray diffraction (SXRD). These features endow Cu-Bi2-x Se3 with sufficient specific capacity (320 mA h g-1 at 0.1 A g-1 ), high-rate performance (97 mA h g-1 at 10 A g-1 ), and reliable cycling stability (70 mA h g-1 at 10 A g-1 after 4000 cycles). Furthermore, quasi-solid-state fiber-shaped ZIBs employing the Cu-Bi2-x Se3 cathode demonstrate respectable performance and superior flexibility even under high mass loading. This work implements a conceptually innovative strategy represented by cation defect design in topological insulator cathode for achieving high-performance battery electrochemistry.

A deep-learning system to help make the surgical planning of coil embolization for unruptured intracranial aneurysms.

BACKGROUND: Coil embolization is a common method for treating unruptured intracranial aneurysms (UIAs). To effectively perform coil embolization for UIAs, clinicians must undergo extensive training with the assistance of senior physicians over an extended period. This study aimed to establish a deep-learning system for measuring the morphological features of UIAs and help the surgical planning of coil embolization for UIAs. METHODS: Preoperative computational tomography angiography (CTA) data and surgical data from UIA patients receiving coil embolization in our medical institution were retrospectively reviewed. A convolutional neural network (CNN) model was trained on the preoperative CTA data, and the morphological features of UIAs were measured automatically using this CNN model. The intraclass correlation coefficient (ICC) was utilized to examine the similarity between the morphologies measured by the CNN model and those determined by experienced clinicians. A deep neural network model to determine the diameter of first coil was further established based on the CNN model within the derivation set (75% of all patients) using neural factorization machines (NFM) model and was validated using a validation set (25% of all patients). The general match ratio (the difference was within ± 1 mm) between the predicted diameter of first coil by model and that used in practical scenario was calculated. RESULTS: One-hundred fifty-three UIA patients were enrolled in this study. The CNN model could diagnose UIAs with an accuracy of 0.97. The performance of this CNN model in measuring the morphological features of UIAs (i.e., size, height, neck diameter, dome diameter, and volume) was comparable to the accuracy of senior clinicians (all ICC > 0.85). The diameter of first coil predicted by the model established based on CNN model and the diameter of first coil used actually exhibited a high general match ratio (0.90) within the derivation set. Moreover, the model performed well in recommending the diameter of first coil within the validation set (general match ratio as 0.91). CONCLUSION: This study presents a deep-learning system which can help to improve surgical planning of coil embolization for UIAs.

Discovery of novel salicylaldehyde derivatives incorporating an α-methylene-γ-butyrolactone moiety as fungicidal agents.

BACKGROUND: Plant diseases caused by phytopathogenic fungi and oomycetes pose a serious threat to ensuring crop yield and quality. Finding novel fungicidal candidates based on natural products is one of the critical methods for developing effective and environmentally friendly pesticides. In this study, a series of salicylaldehyde derivatives containing an α-methylene-γ-butyrolactone moiety were designed, synthesized, and their fungicidal activities were evaluated. RESULTS: The bioassay studies indicated that compound C3 displayed an excellent in vitro activity against Rhizoctonia solani with a half-maximal effective concentration (EC50 ) value of 0.65 µg/mL, higher than that of pyraclostrobin (EC50 = 1.44 µg/mL) and comparable to that of carbendazim (EC50 = 0.33 µg/mL). For Valsa mali and Phytophthora capsici, compound C3 also showed good fungicidal activities with EC50 values of 0.91 and 1.33 µg/mL, respectively. In addition, compound C3 exhibited promising protective in vivo activity against R. solani (84.1%) at 100 µg/mL, which was better than that of pyraclostrobin (78.4%). The pot experiment displayed that compound C3 had 74.8% protective efficacy against R. solani at 200 µg/mL, which was comparable to that of validamycin (78.2%). The antifungal mode of action research indicated that compound C3 could change the mycelial morphology and ultrastructure, increase cell membrane permeability, affect respiratory metabolism by binding to complex III, and inhibit the germination and formation of sclerotia, thereby effectively controlling the disease. CONCLUSION: The present study provides support for the application of these salicylaldehyde derivatives as promising potential pesticides with remarkable and broad-spectrum fungicidal activities against phytopathogenic fungi and oomycetes in crop protection. © 2023 Society of Chemical Industry.

Pipeline versus Tubridge in the treatment of unruptured posterior circulation aneurysms.

BACKGROUND: To compare the safety and efficacy of pipeline embolization device (PED) and Tubridge flow diverter (TFD) for unruptured posterior circulation aneurysms. METHODS: Posterior aneurysm patients treated with PED or TFD between January, 2019, and December, 2021, were retrospectively reviewed. Patients' demographics, aneurysm characteristics, treatment details, complications, and follow-up information were collected. The procedural-related complications and angiographic and clinical outcome were compared. RESULTS: A total of 107 patients were involved; PED was applied for 55 patients and TFD for 52 patients. A total of 9 (8.4%) procedural-related complications occurred, including 4 (7.3%) in PED group and 5 (9.6%) in TFD group. During a mean of 10.3-month angiographic follow-up for 81 patients, complete occlusion was achieved in 35 (85.4%) patients in PED group and 30 (75.0%) in TFD group. The occlusion rate of PED group is slightly higher than that of TFD group. A mean of 25.0-month clinical follow-up for 107 patients showed that favorable clinical outcome was achieved in 53 (96.4%) patients in PED group and 50 (96.2%) patients in TFD group, respectively. No statistical difference was found in terms of procedural-related complications (p = 0.737), occlusion rate (p = 0.241), and favorable clinical outcome (0.954) between groups. CONCLUSIONS: The current study found no difference in complication, occlusion, and clinical outcome between PED and TFD for unruptured PCAs.

Model based on single-nucleotide polymorphism to discriminate aspirin resistance patients.

BACKGROUND: Aspirin is widely used for preventing ischaemic events. About 20%-40% of patients have aspirin resistance (ASR), which prevents them from benefiting from aspirin medication. This study aimed to develop and validate a model based on single-nucleotide polymorphism (SNP) to distinguish ASR patients. METHODS: We included patients with spontaneous intracerebral haemorrhage and continuing antiplatelet therapy from a multicentre, prospective cohort study as the derivation cohort. Thromboelastography (inhibition of arachidonic acid channel<50%) was used to identify ASR. Genotyping was performed to identify the ASR-related SNP. Based on the result of the logistic analysis, the aspirin resistance in the Chinese population score (ASR-CN score) was established, and its accuracy was evaluated using the area under the curve (AUC). Patients receiving dual antiplatelet therapy for unruptured intracranial aneurysm embolism were prospectively included in the validation cohort. After embolism, 30-day ischaemic events, including ischaemic stroke, new or more frequent transient ischaemic attack, stent thrombosis and cerebrovascular death, were recorded. RESULTS: The derivation cohort included 212 patients (155 male patients and the median age as 59). 87 (41.0%) individuals were identified with ASR. The multivariate logistic analysis demonstrated six SNPs of GP1BA, TBXA2R, PTGS2 and NOS3 as risk factors related to ASR. The ASR-CN score integrating these SNPs performed well to discriminate ASR patients from non-ASR patients (AUC as 0.77). Based on the validation cohort of 372 patients receiving antiplatelet therapy after embolism (including 130 ASR patients), the ASR-CN score continued to distinguish ASR patients with good accuracy (AUC as 0.80). Patients with high a ASR-CN score were more likely to suffer from 30-day ischaemic events after embolism (OR, 1.28; 95% CI, 1.10 to 1.50; p=0.002). CONCLUSION: GP1BA, TBXA2R, PTGS2 and NOS3 were SNPs related to ASR. The ASR-CN score is an effective tool to discriminate ASR patients, which may guide antiplatelet therapy. CLINICAL TRIAL REGISTRATION: Surgical Treatments of Antiplatelet Intracerebral Hemorrhage cohort (unique identifier: ChiCTR1900024406, http://www.chictr.org.cn/edit.aspx?pid=40640&htm=4).

Fabrication and Characterization of Polylactic Acid Electrospun Wound Dressing Modified with Polyethylene Glycol, Rosmarinic Acid and Graphite Oxide.

Polylactic acid (PLA) is a biodegradable polymer made from natural sources, and its electrospinning (e-spinning) nanofiber membrane doped with antibacterial ingredients is widely used in the field of medical dressings. In this research, 9 wt% of rosmarinic acid (RosA) and 0.04 wt% of graphite oxide (GO) with synergistic antibacterial activity were introduced into the e-spinning PLA precursor solution, and the obtained PLA nanofiber membrane showed good antibacterial properties and wound healing effects. At the same time, a nonionic amphiphilic polymer, polyethylene glycol (PEG), was also introduced into this system to improve the hydrophilicity of the e-spinning membrane for wound healing application. The morphological characterization showed the RosA/GO and PEG did not affect the e-spinning of PLA. The tests of mechanical performance and wettability demonstrated that PEG and RosA/GO incorporated in PLA have migrated easily to the surface of the fiber. The e-spun PLA/PEG/RosA/GO membrane showed good antibacterial activity and promoted initial wound healing quickly, which would be a promising application in wound dressing.

Furofuran Lignans for Plant Protection: Discovery of Sesamolin and Its Derivatives as Novel Anti-Tobacco Mosaic Virus and Antibacterial Agents.

Natural products have been a valuable source of efficient and low-risk pesticides. In this work, a series of novel sesamolin derivatives A0-A31 and B0-B4 were designed and synthesized via structural simplification of furofuran lignan phrymarolin II, and their antiviral and antibacterial activities were systematically evaluated. The bioassay results showed that compound A24 displayed remarkable inactivation activity against tobacco mosaic virus (TMV) with an EC50 value of 130.4 µg/mL, which was superior to that of commercial ningnanmycin (EC50 = 202.0 µg/mL). The antiviral mode of action assays suggested that compound A24 may obstruct self-assembly by binding to TMV coat protein (CP), thus resisting the TMV infection. In addition, compound A25 possessed prominent antibacterial activities, especially against Ralstonia solanacearum with an EC50 value of 43.8 µg/mL, which is better than those of commercial bismerthiazol and thiodiazole copper. This research lays a solid foundation for the utilization of furofuran lignans in crop protection.

Intercropping Sedum alfredii Hance and Cicer arietinum L. does not present a suitable land use pattern for multi-metal-polluted soil.

Intercropping of specific accumulators with industrial crops is used in moderately metal contaminated agricultural land. The distribution characteristics and environmental risks of non-accumulated ions in intercropping fields have rarely been reported. This study analyzed dissolved organic matter (DOM) fractionation and metal chemical forms to investigate the bioavailability, transformation, and uptake of non-hyperaccumulated metals in different cultivation patterns of a Cd hyperaccumulator (Sedum alfredii Hance) and a commercial crop (Cicer arietinum L.). The study focused on the distribution and transformation of heavy metals, with a particular emphasis on the role of DOM in intercropping. The contents of DOM in the rhizosphere soils of the Cd hyperaccumulator monoculture and the intercropping field were obviously greater than the DOM concentration in the commercial crop monoculture. The content of soluble Cd was significantly lower in the former two planting patterns than in the latter. In contrast, soluble Pb and Cu exhibited opposite content characteristics. In addition, the metal extraction ability of DOM extracted from the C. arietinum monoculture was lower than those from the Cd hyperaccumulator monoculture and the intercropping field. The concentrations of Cd in both below-ground and aerial parts of C. arietinum intercropping were significantly lower than those in its monoculture, since S. alfredii depleted soil Cd. Contrastingly, the contents of Cu and Pb in C. arietinum harvested from intercropping were significantly greater than those in its monoculture because the intercropped Cd hyperaccumulator activated Cu and Pb by changing soil DOM content and fractionations without absorbing them. The findings provide valuable insights into the use of intercropping to remediate moderately metal-contaminated agricultural land and highlight the potential risks associated with intercropping in multi-metal-contaminated fields.

Evolution and Discovery of Matrine Derivatives as a New Class of Anti-Hepatic Fibrosis Agents Targeting Ewing Sarcoma Breakpoint Region 1 (EWSR1).

A series of new tricyclic matrinane derivatives were continuously synthesized and evaluated for their inhibitory effects on genes and proteins related to hepatic fibrosis at the cellular level, including collagen type I α1 chain (COL1A1), α smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and matrix metalloprotein 2 (MMP-2). Among them, compound 6k exerted an appealing potency and significantly reduced liver injury and fibrosis in both bile duct ligation (BDL) rats and Mdr2 knockout mice. An activity-based protein profiling (ABPP) assay indicated that 6k might directly bind to Ewing sarcoma breakpoint region 1 (EWSR1) to inhibit its function and affect the expression of downstream liver fibrosis-related genes and thus regulate liver fibrosis. These results provided a potential novel target for the treatment of liver fibrosis and powerful information for the development of tricyclic matrinanes into promising anti-hepatic fibrosis agents.

The Moral Foundations of Vaccine Passports.

The debate around vaccine passports has been polarising and controversial. Although the measure allows businesses to resume in-person operations and enables transitioning out of lockdown due to the COVID-19 pandemic, some have expressed concerns about liberty violations and discrimination. Understanding the splintered viewpoints can aid businesses in communicating such measures to employees and consumers. We conceptualise the business implementation of vaccine passports as a moral decision rooted in individual values that influence reasoning and emotional reaction. We surveyed support for vaccine passports on a nationally representative sample in the United Kingdom in 2021: April (n = 349), May (n = 328), and July (n = 311). Drawing on the Moral Foundations Theory-binding (loyalty, authority, and sanctity), individualising (fairness and harm), and liberty values-we find that individualising values are a positive predictor and liberty values a negative predictor of support for passports, suggesting adoption hinges on addressing liberty concerns. Longitudinal analysis examining the trajectory of change in support over time finds that individualising foundations positively predict changes in utilitarian and deontological reasoning over time. In contrast, a fall in anger over time predicts increased support towards vaccine passports. Our study can inform business and policy communication strategies of existing vaccine passports, general vaccine mandates, and similar measures in future pandemics.

Structure Optimization of 12ß-O-γ-Glutamyl Oleanolic Acid Derivatives Resulting in Potent FXR Antagonist/Modulator for NASH Therapy.

The farnesoid X receptor (FXR) plays a crucial role in regulating the metabolism of bile acids, lipids, and sugars. Consequently, it is implicated in the treatment of various diseases, including cholestasis, diabetes, hyperlipidemia, and cancer. The advancement of novel FXR modulators holds immense importance, especially in managing metabolic disorders. In this study, a series of oleanolic acid (OA) derivatives bearing 12ß-O-(γ-glutamyl) groups were designed and synthesized. Using a yeast one-hybrid assay, we established a preliminary structure-activity relationship (SAR) and identified the most potent compound, 10b, which selectively antagonizes FXR over other nuclear receptors. Compound 10b can differentially modulate the downstream genes of FXR, including with the upregulation of the CYP7A1 gene. In vivo testing revealed that 10b (100 mg·Kg-1) not only effectively inhibits lipid accumulation in the liver but also prevents liver fibrosis in both BDL rats and HFD mice. Molecular modeling indicated that the branched substitution of 10b extends into the H11-H12 region of FXR-LBD, possibly accounting for its CYP7A1 upregulation, which is different from a known OA 12ß-alkonate. These findings suggest that 12-glutamyl OA derivative 10b represents a promising candidate for the treatment of nonalcoholic steatohepatitis (NASH).