Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PLP), a traditional Chinese medicine, is recognized for its antioxidative and anti-apoptotic properties. Despite its potential medicinal value, the mechanisms underlying its efficacy have been less explored, particularly in alleviating acute liver injury (ALI) caused by excessive intake of acetaminophen (APAP). AIM OF THE STUDY: This study aims to elucidate the role and mechanisms of PLP in mitigating oxidative stress and apoptosis induced by APAP. MATERIALS AND METHODS: C57BL/6 male mice were pre-treated with PLP for seven consecutive days, followed by the induction of ALI using APAP. Liver pathology was assessed using HE staining. Serum indicators, immunofluorescence (IF), immunohistochemical (IHC), and transmission electron microscopy were employed to evaluate levels of oxidative stress, ferroptosis and apoptosis. Differential expression proteins (DEPs) in the APAP-treated and PLP pre-treated groups were analyzed using quantitative proteomics. Subsequently, the potential mechanisms of PLP pre-treatment in treating ALI were validated using western blotting, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) analysis. RESULTS: The UHPLC assay confirmed the presence of three compounds, i.e., albiflorin, paeoniflorin, and oxypaeoniflorin. Pre-treatment with PLP was observed to ameliorate liver tissue pathological damage through HE staining. Further confirmation of efficacy of PLP in alleviating APAP-induced liver injury and oxidative stress was established through liver function serum biochemical indicators, IF of reactive oxygen species (ROS) and IHC of glutathione peroxidase 4 (GPX4) detection. However, PLP did not demonstrate a significant effect in alleviating APAP-induced ferroptosis. Additionally, transmission electron microscopy and TUNEL staining indicated that PLP can mitigate hepatocyte apoptosis. PKC-ERK pathway was identified by proteomics, and subsequent molecular docking, molecular dynamics simulations, and SPR verified binding of the major components of PLP to ERK protein. Western blotting demonstrated that PLP suppressed protein kinase C (PKC) phosphorylation, blocking extracellular signal-regulated kinase (ERK) phosphorylation and inhibiting oxidative stress and cell apoptosis. CONCLUSION: This study demonstrates that PLP possesses hepatoprotective abilities against APAP-induced ALI, primarily by inhibiting the PKC-ERK cascade to suppress oxidative stress and cell apoptosis.

Therapeutic effects of epigallocatechin-3-gallate for inflammatory bowel disease: A preclinical meta-analysis.

BACKGROUND: Epigallocatechin-3-gallate (EGCG), the primary active compound in green tea, is recognized for its significant anti-inflammatory properties and potential pharmacological effects on inflammatory bowel disease (IBD). However, comprehensive preclinical evidence supporting the use of EGCG in treating IBD is currently insufficient. PURPOSE: To evaluate the efficacy of EGCG in animal models of IBD and explore potential underlying mechanisms, serving as a groundwork for future clinical investigations. METHODS: A systematic review of pertinent preclinical studies published until September 1, 2023, in databases such as PubMed, Embase, Web of Science, and Cochrane Library was conducted, adhering to stringent quality criteria. The potential mechanisms via which EGCG may address IBD were summarized. STATA v16.0 was used to perform a meta-analysis to assess IBD pathology, inflammation, and indicators of oxidative stress. Additionally, dose-response analysis and machine learning models were utilized to evaluate the dose-effect relationship and determine the optimal dosage of EGCG for IBD treatment. RESULTS: The analysis included 19 studies involving 309 animals. The findings suggest that EGCG can ameliorate IBD-related pathology in animals, with a reduction in inflammatory and oxidative stress indicators. These effects were observed through significant changes in histological scores, Disease Activity Index, Colitis Macroscopic Damage Index and colon length; a decrease in markers such as interleukin (IL)-1ß, IL-6 and interferon-γ; and alterations in malondialdehyde, superoxide dismutase, glutathione, and catalase levels. Subgroup analysis indicated that the oral administration route of EGCG exhibited superior efficacy over other administration routes. Dose-response analysis and machine learning outcomes highlighted an optimal EGCG dosage range of 32-62 mg/kg/day, with an intervention duration of 4.8-13.6 days. CONCLUSIONS: EGCG exhibits positive effects on IBD, particularly when administered at the dose range of 32 - 62 mg/kg/day, primarily attributed to its ability to regulate inflammation and oxidative stress levels.

Subscaling of a cytosolic RNA binding protein governs cell size homeostasis in the multiple fission alga Chlamydomonas.

Coordination of growth and division in eukaryotic cells is essential for populations of proliferating cells to maintain size homeostasis, but the underlying mechanisms that govern cell size have only been investigated in a few taxa. The green alga Chlamydomonas reinhardtii (Chlamydomonas) proliferates using a multiple fission cell cycle that involves a long G1 phase followed by a rapid series of successive S and M phases (S/M) that produces 2n daughter cells. Two control points show cell-size dependence: the Commitment control point in mid-G1 phase requires the attainment of a minimum size to enable at least one mitotic division during S/M, and the S/M control point where mother cell size governs cell division number (n), ensuring that daughter distributions are uniform. tny1 mutants pass Commitment at a smaller size than wild type and undergo extra divisions during S/M phase to produce small daughters, indicating that TNY1 functions to inhibit size-dependent cell cycle progression. TNY1 encodes a cytosolic hnRNP A-related RNA binding protein and is produced once per cell cycle during S/M phase where it is apportioned to daughter cells, and then remains at constant absolute abundance as cells grow, a property known as subscaling. Altering the dosage of TNY1 in heterozygous diploids or through mis-expression increased Commitment cell size and daughter cell size, indicating that TNY1 is a limiting factor for both size control points. Epistasis placed TNY1 function upstream of the retinoblastoma tumor suppressor complex (RBC) and one of its regulators, Cyclin-Dependent Kinase G1 (CDKG1). Moreover, CDKG1 protein and mRNA were found to over-accumulate in tny1 cells suggesting that CDKG1 may be a direct target of repression by TNY1. Our data expand the potential roles of subscaling proteins outside the nucleus and imply a control mechanism that ties TNY1 accumulation to pre-division mother cell size.

Selectivity Control by Relay Catalysis in CO and CO2 Hydrogenation to Multicarbon Compounds.

ConspectusThe hydrogenative conversion of both CO and CO2 into high-value multicarbon (C2+) compounds, such as olefins, aromatic hydrocarbons, ethanol, and liquid fuels, has attracted much recent attention. The hydrogenation of CO is related to the chemical utilization of various carbon resources including shale gas, biomass, coal, and carbon-containing wastes via syngas (a mixture of H2 and CO), while the hydrogenation of CO2 by green H2 to chemicals and liquid fuels would contribute to recycling CO2 for carbon neutrality. The state-of-the-art technologies for the hydrogenation of CO/CO2 to C2+ compounds primarily rely on a direct route via Fischer-Tropsch (FT) synthesis and an indirect route via two methanol-mediated processes, i.e., methanol synthesis from CO/CO2 and methanol to C2+ compounds. The direct route would be more energy- and cost-efficient owing to the reduced operation units, but the product selectivity of the direct route via FT synthesis is limited by the Anderson-Schulz-Flory (ASF) distribution. Selectivity control for the direct hydrogenation of CO/CO2 to a high-value C2+ compound is one of the most challenging goals in the field of C1 chemistry, i.e., chemistry for the transformation of one-carbon (C1) molecules.We have developed a relay-catalysis strategy to solve the selectivity challenge arising from the complicated reaction network in the hydrogenation of CO/CO2 to C2+ compounds involving multiple intermediates and reaction channels, which inevitably lead to side reactions and byproducts over a conventional heterogeneous catalyst. The core of relay catalysis is to design a single tandem-reaction channel, which can direct the reaction to the target product controllably, by choosing appropriate intermediates (or intermediate products) and reaction steps connecting these intermediates, and arranging optimized yet matched catalysts to implement these steps like a relay. This Account showcases representative relay-catalysis systems developed by our group in the past decade for the synthesis of liquid fuels, lower (C2-C4) olefins, aromatics, and C2+ oxygenates from CO/CO2 with selectivity breaking the limitation of conventional catalysts. These relay systems are typically composed of a metal or metal oxide for CO/CO2/H2 activation and a zeolite for C-C coupling or reconstruction, as well as a third or even a fourth catalyst component with other functions if necessary. The mechanisms for the activation of H2 and CO/CO2 on metal oxides, which are distinct from that on the conventional transition or noble metal surfaces, are discussed with emphasis on the role of oxygen vacancies. Zeolites catalyze the conversion of intermediates (including hydrocracking/isomerization of heavier hydrocarbons, methanol-to-hydrocarbon reactions, and carbonylation of methanol/dimethyl ether) in the relay system, and the selectivity is mainly controlled by the Brønsted acidity and the shape-selectivity or the confinement effect of zeolites. We demonstrate that the thermodynamic/kinetic matching of the relay steps, the proximity and spatial arrangement of the catalyst components, and the transportation of intermediates/products in sequence are the key issues guiding the selection of each catalyst component and the construction of an efficient relay-catalysis system. Our methodology would also be useful for the transformation of other C1 molecules via controlled C-C coupling, inspiring more efforts toward precision catalysis.

Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis.

Background: Pathological progression from non-alcoholic fatty liver disease (NAFLD) to liver fibrosis (LF) to hepatocellular carcinoma (HCC) is a common dynamic state in many patients. Curcumin, a dietary supplement derived from the turmeric family, is expected to specifically inhibit the development of this progression. However, there is a lack of convincing evidence. Methods: The studies published until June 2023 were searched in PubMed, Web of Science, Embase, and the Cochrane Library databases. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) approach was used to evaluate the certainty of evidence. StataSE (version 15.1) and Origin 2021 software programs were used to analyze the critical indicators. Results: Fifty-two studies involving 792 animals were included, and three disease models were reported. Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD, liver fibrosis, and HCC. We conducted a detailed analysis of common inflammatory markers IL-1ß, IL-6, and TNF-α, which traverse the entire disease process. The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/kg and treatment duration from 4 to 10 weeks. The mechanistic analysis reveals that curcumin primarily exerts its hepatoprotective effects by modulating multiple signaling pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3, and TGF-ß/Smad3. Conclusion: In summary, curcumin has shown promising therapeutic effects during the overall progression of NAFLD-LF-HCC. It inhibited the pathological progression by synergistic mechanisms related to multiple pathways, including anti-inflammatory, antioxidant, and apoptosis regulation.

Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives.

Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer-related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy-related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy-modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/ß-catenin, Beclin-1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double-edged sword in HCC management.

Recent Advances of Benzodithiophene-Based Donor Materials for Organic Solar Cells.

Recently, the power conversion efficiency (PCE) of organic solar cells (OSCs) has increased dramatically, making a big step toward the industrial application of OSCs. Among numerous OSCs, benzodithiophene (BDT)-based OSCs stand out in achieving efficient PCE. Notably, single-junction OSCs using BDT-based polymers as donor materials have completed a PCE of over 19%, indicating a dramatic potential for preparing high-performance large-scale OSCs. This paper reviews the recent progress of OSCs based on BDT polymer donor materials (PDMs). The development of BDT-based OSCs is concisely summarized. Meanwhile, the relationship between the structure of PDMs and the performance of OSCs is further described in this review. Besides, the development and prospect of single junction OSCs are also discussed.

N-Type Small Molecule Electron Transport Layers with Excellent Surface Energy and Moisture Resistance Siloxane for Non-Fullerene Organic Solar Cells.

Electron transport layers (ETLs) generally contain polar groups for enhancing performance and reducing the work function. Nevertheless, the polar group with high surface energy may cause inferior interfacial compatibility, which challenges the ETLs to balance stability and performance. Here, two conjugated small molecules of ETLs with low surface energy siloxane, namely PDI-Si and PDIN-Si, are synthesized. The siloxane with low surface energy not only enhances the interfacial compatibility between ETLs and active layers but also improves the moisture-proof stability of the device. Impressively, the amine-functionalized PDIN-Si can simultaneously exhibit conspicuous n-type self-doping properties and outstanding moisture-proof stability. The optimization of interfacial contact and morphology enables the PM6:Y6-based OSC with PDIN-Si to achieve a power conversion efficiency (PCE) of 15.87%, which is slightly superior to that of classical ETL PDINO devices (15.27%), and when the PDIN-Si film thickness reaches 28 nm, the PCE remains at 13.19% (≈83%), which indicates that PDIN-Si has satisfactory thickness insensitivity to facilitate roll-to-roll processing. Excitingly, after 120 h of storage in an environment with humidity above 45%, the unencapsulated device with PDIN-Si as ETL remains at 75% of the initial PCE value, while the device with PDINO as ETL is only 50%.

Deciphering the toxicity-effect relationship and action patterns of traditional Chinese medicines from a smart data perspective: a comprehensive review.

In Chinese medicine, the primary considerations revolve around toxicity and effect. The clinical goal is to achieve maximize effect while minimizing toxicity. Nevertheless, both clinical and experimental research has revealed a distinct relationship between these two patterns of action in toxic Traditional Chinese Medicines (TCM). These TCM often exhibit characteristic "double-sided" or "multi-faceted" features under varying pathological conditions, transitioning between effective and toxic roles. This complexity adds a layer of challenge to unraveling the ultimate objectives of Traditional Chinese medicine. To address this complexity, various hypotheses have been proposed to explain the toxicity and effect of Traditional Chinese Medicines. These hypotheses encompass the magic shrapnel theory for effect, the adverse outcome pathway framework, and the indirect toxic theory for toxicity. This review primarily focuses on high-, medium-, and low-toxicity Traditional Chinese Medicines as listed in Chinese Pharmacopoeia. It aims to elucidate the essential intrinsic mechanisms and elements contributing to their toxicity and effectiveness. The critical factors influencing the mechanisms of toxicity and effect are the optimal dosage and duration of TCM administration. However, unraveling the toxic-effect relationships in TCM presents a formidable challenge due to its multi-target and multi-pathway mechanisms of action. We propose the integration of multi-omics technology to comprehensively analyze the fundamental metabolites, mechanisms of action, and toxic effects of TCM. This comprehensive approach can provide valuable insights into the intricate relationship between the effect and toxicity of these TCM.

Integrative evidence construction for resveratrol treatment of nonalcoholic fatty liver disease: preclinical and clinical meta-analyses.

Background: Resveratrol, a polyphenol found in various plants, is known for its diverse bioactivities and has been explored in relation to nonalcoholic fatty liver disease (NAFLD). However, no high-quality evidence exists regarding its efficacy. Objective: a meta-analysis was conducted to evaluate the potential efficacy of resveratrol in treating nonalcoholic fatty liver disease by analyzing both preclinical studies and clinical trials. Method: PubMed, Embase and Web of Science were searched for the included literature with the criteria for screening. Quantitative synthesis and meta-analyses were performed by STATA 16.0. Results: Twenty-seven studies were included, and the results indicated that resveratrol effectively improved liver function, reduced fatty liver indicators, and affected other indices in preclinical studies. The effective dosage ranged from 50 mg/kg-200 mg/kg, administered over a period of 4-8 weeks. While there were inconsistencies between clinical trials and preclinical research, both study types revealed that resveratrol significantly reduced tumor necrosis factor-α levels, further supporting its protective effect against nonalcoholic fatty liver disease. Additionally, resveratrol alleviated nonalcoholic fatty liver disease primarily via AMPK/Sirt1 and anti-inflammatory signaling pathways. Conclusion: Current meta-analysis could not consistently verify the efficacy of resveratrol in treating nonalcoholic fatty liver disease, but demonstrated the liver-protective effects on nonalcoholic fatty liver disease. The large-sample scale and single region RCTs were further needed to investigate the efficacy.

Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery.

Proper repair of DNA damage lesions is essential to maintaining genome integrity and preventing the development of human diseases, including cancer. Increasing evidence suggests the importance of the nuclear envelope in the spatial regulation of DNA repair, although the mechanisms of such regulatory processes remain poorly defined. Through a genome-wide synthetic viability screen for PARP-inhibitor resistance using an inducible CRISPR-Cas9 platform and BRCA1-deficient breast cancer cells, we identified a transmembrane nuclease (renamed NUMEN) that could facilitate compartmentalized and non-homologous end joining-dependent repair of double-stranded DNA breaks at the nuclear periphery. Collectively, our data demonstrate that NUMEN generates short 5' overhangs through its endonuclease and 3'→5' exonuclease activities, promotes the repair of DNA lesions-including heterochromatic lamina-associated domain breaks as well as deprotected telomeres-and functions as a downstream effector of DNA-dependent protein kinase catalytic subunit. These findings underline the role of NUMEN as a key player in DNA repair pathway choice and genome-stability maintenance, and have implications for ongoing research into the development and treatment of genome instability disorders.

Crosstalk between colorectal cancer cells and cancer-associated fibroblasts in the tumor microenvironment mediated by exosomal noncoding RNAs.

Colorectal cancer (CRC) is a common malignant tumor of the digestive system, and its morbidity rates are increasing worldwide. Cancer-associated fibroblasts (CAFs), as part of the tumor microenvironment (TME), are not only closely linked to normal fibroblasts, but also can secrete a variety of substances (including exosomes) to participate in the regulation of the TME. Exosomes can play a key role in intercellular communication by delivering intracellular signaling substances (e.g., proteins, nucleic acids, non-coding RNAs), and an increasing number of studies have shown that non-coding RNAs of exosomal origin from CAFs are not only closely associated with the formation of the CRC microenvironment, but also increase the ability of CRC to grow in metastasis, mediate tumor immunosuppression, and are involved in the mechanism of drug resistance in CRC patients receiving. It is also involved in the mechanism of drug resistance after radiotherapy in CRC patients. In this paper, we review the current status and progress of research on CAFs-derived exosomal non-coding RNAs in CRC.

Synthetic Biology Pathway to Nucleoside Triphosphates for Expanded Genetic Alphabets.

One horizon in synthetic biology seeks alternative forms of DNA that store, transcribe, and support the evolution of biological information. Here, hydrogen bond donor and acceptor groups are rearranged within a Watson-Crick geometry to get 12 nucleotides that form 6 independently replicating pairs. Such artificially expanded genetic information systems (AEGIS) support Darwinian evolution in vitro. To move AEGIS into living cells, metabolic pathways are next required to make AEGIS triphosphates economically from their nucleosides, eliminating the need to feed these expensive compounds in growth media. We report that "polyphosphate kinases" can be recruited for such pathways, working with natural diphosphate kinases and engineered nucleoside kinases. This pathway in vitro makes AEGIS triphosphates, including third-generation triphosphates having improved ability to survive in living bacterial cells. In α-32P-labeled forms, produced here for the first time, they were used to study DNA polymerases, finding cases where third-generation AEGIS triphosphates perform better with natural enzymes than second-generation AEGIS triphosphates.

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives.

Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi-phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK-related signaling pathways, p53 signaling pathway, ER stress, Caspase-8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area.

Protective role of baicalin in the dynamic progression of lung injury to idiopathic pulmonary fibrosis: A meta-analysis.

BACKGROUND AND PURPOSE: The pathological progression of lung injury (LI) to idiopathic pulmonary fibrosis (IPF) is a common feature of the development of lung disease. At present, effective strategies for preventing this progression are unavailable. Baicalin has been reported to specifically inhibit the progression of LI to IPF. Therefore, this meta-analysis aimed to assess its clinical application and its potential as a therapeutic drug for lung disease based on integrative analysis. METHODS: We systematically searched preclinical articles in eight databases and reviewed them subjectively. The CAMARADES scoring system was used to assess the degree of bias and quality of evidence, whereas the STATA software (version 16.0 software) was used for statistical analysis, including a 3D analysis of the effects of dosage frequency of baicalin in LI and IPF. The protocol of this meta-analysis is documented in the PROSPERO database (CRD42022356152). RESULTS: A total of 23 studies and 412 rodents were included after several rounds of screening. Baicalin was found to reduce the levels of TNF-α, IL-1ß, IL-6, HYP, TGF-ß and MDA and the W/D ratio and increase the levels of SOD. Histopathological analysis of lung tissue validated the regulatory effects of baicalin, and the 3D analysis of dosage frequency revealed that the effective dose of baicalin is 10-200 mg/kg. Mechanistically, baicalin can prevent the progression of LI to IPF by modulating p-Akt, p-NF-κB-p65 and Bcl-2-Bax-caspase-3 signalling. Additionally, baicalin is involved in signalling pathways closely related to anti-apoptotic activity and regulation of lung tissue and immune cells. CONCLUSION: Baicalin at the dose of 10-200 mg/kg exerts protective effects against the progression of LI to IPF through anti-inflammatory and anti-apoptotic pathways.

Ultrasound computed tomography based on full waveform inversion with source directivity calibration.

Ultrasound computed tomography based on full waveform inversion has the potential to provide high-resolution images of human tissues in a quantitative manner. A successful ultrasound computed tomography system requires the decent knowledge of acquisition array, including the spatial position and the directivity of each transducer, to meet the high-level demand of clinical applications. The conventional full waveform inversion algorithm assumes a point source with the omni-directional emission. Such assumption does not hold when the directivity of emitting transducer is not negligible. For a practical implementation, an efficient and accurate self-checking evaluation of directivity is crucial prior to the reconstruction of images. We propose to measure the directivity of each emitting transducer using the full-matrix captured data obtained with a water-immersed and target-free experiment. We introduce the weighted virtual point-source array to act as the proxy of emitting transducer during the numerical simulation. The weights of different points in the virtual array can be calculated from the observed data using the gradient-based local optimization method. Although the full waveform imaging method relies on the finite-difference solver of wave equation, such directivity estimation benefits from the introduction of analytical solver. The trick significantly reduces the numerical cost, enabling an automatic directivity self-check at boot. We verify the feasibility, efficiency, and accuracy of the virtual array method through simulated and experimental tests. For the experimental test, we also illustrate that full waveform inversion with directivity calibration can reduce the artifacts introduced by the conventional point source assumption, improving the quality of reconstructed images..

The effect of gastric bypass surgery on cognitive function of Alzheimer's disease and the role of GLP1-SGLT1 pathway.

OBJECTIVE: Gastric bypass surgery has been shown to improve metabolic profiles via GLP1, which may also have cognitive benefits for Alzheimer's disease (AD) patients. However, the exact mechanism requires further investigation. METHODS: Roux-en-Y gastric bypass or sham surgery was performed on APP/PS1/Tau triple transgenic mice (an AD mice model) or wild type C57BL/6 mice. Morris Water Maze (MWM) test was used to evaluate the cognitive function of mice and animal tissue samples were obtained for measurements two months after the surgery. Additionally, STC-1 intestine cells were treated with siTAS1R2 and siSGLT1, and HT22 nerve cells were treated with Aß, siGLP1R, GLP1 and siSGLT1 in vitro to explore the role of GLP1-SGLT1 related signaling pathway in cognitive function. RESULTS: The MWM test showed that bypass surgery significantly improved cognitive function in AD mice as measured by navigation and spatial probe tests. Moreover, bypass surgery reversed neurodegeneration, down-regulated hyperphosphorylation of Tau protein and Aß deposition, improved glucose metabolism, and up-regulated the expression of GLP1, SGLT1, and TAS1R2/3 in the hippocampus. Furthermore, GLP1R silencing down-regulated SGLT1 expression, whereas SGLT1 silencing increased Tau protein deposition and exacerbated dysregulated of glucose metabolism in HT22 cells. However, RYGB did not alter the level of GLP1 secretion in the brainstem (where central GLP1 is mainly produced). Additionally, GLP1 expression was upregulated by RYGB via TAS1R2/3-SGLT1 activation sequentially in the small intestine. CONCLUSION: RYGB surgery could improve cognition function in AD mice through facilitating glucose metabolism and reducing Tau phosphorylation and Aß deposition in the hippocampus, mediated by peripheral serum GLP1 activation of SGLT1 in the brain. Furthermore, RYGB increased GLP1 expression through sequential activation of TAS1R2/TAS1R3 and SGLT1 in the small intestine.

Bay-Functionalized Perylene Diimide Derivative Cathode Interfacial Layer for High-Performance Organic Solar Cells.

The field of organic solar cells (OSCs) has acquired rapid progress with the development of nonfullerene acceptors. Interfacial engineering is also significant for the enhancement of the power conversion efficiency (PCE) in OSCs. Among the cathode interfacial materials (CIMs), perylene diimide (PDI) small molecules are promising owing to the excellent electron affinity and electron mobility. Although the well-known PDINN molecule has excellent properties, it has a high planarity formed by an extensive rigid π-conjugated backbone. Because the PDI molecular backbone has a strong tendency to aggregate, it causes the problem of excessive molecular aggregation and stacking, which directly leads to excessive crystallinity. Proper accumulation is beneficial for charge transport, but oversized crystals formed by overaggregation will hinder charge transport, ultimately affecting the film morphology and charge transport efficiency. Modifying the bay position of PDINN is an effective strategy to reduce the planarity, modulate the molecular aggregation, optimize the morphology, and enhance the charge-collecting efficiency. Therefore, PDINN-S was synthesized from PDINN by substituting the hydrogen with thiophene. The optimal PCE in the PM6:Y6 active layer was 16.18% and remained at 80% of the initial value after 720 h in a glovebox. This provides some guidance for exploring CIMs and preparing large-scale OSCs in the future.

Preclinical and clinical evidence for the treatment of non-alcoholic fatty liver disease with soybean: A systematic review and meta-analysis.

Non-alcoholic fatty liver disease (NAFLD), a prevalent public health issue, involves the accumulation of triglycerides in hepatocytes, which is generally considered to be an early lesion of liver fibrosis and cirrhosis. Thus, the development of treatments for NAFLD is urgently needed. This study explored the preclinical and clinical evidence of soybeans to alleviate NAFLD. Studies indexed in three relevant databases-Web of Science, PubMed, and Embase-between January 2002 and August 2022 were retrieved. A total of 13 preclinical studies and five RCTs that included 212 animals and 260 patients were included in the present analysis. The preclinical analysis showed that liver function indices (AST, SMD = -1.41, p < 0.0001 and ALT, SMD = -1.47, p < 0.0001) were significantly improved in the soybean group compared to the model group, and fatty liver indicators (TG, SMD = -0.78, p < 0.0001; TC, SMD = -1.38, p < 0.0001) and that oxidative stress indices (MDA, SMD = -1.09, p < 0.0001; SOD, SMD = 1.74, p = 0.022) were improved in the soybean group. However, the five RCTs were not entirely consistent with the preclinical results; however, the results confirmed the protective effect on the liver. The results of the clinical RCTs showed that soybean significantly affected liver function, fatty liver, and oxidative stress indicators (ALT, SMD = -0.42, p = 0.006; TG, SMD = -0.31, p = 0.039; MDA, SMD = -0.76, p = 0.007). The current meta-analysis combined preclinical and clinical studies and verified that soybean could protect the liver in NAFLD by regulating lipid metabolism and oxidative stress factors via the Akt/AMPK/PPARα signaling pathway. Soybean might be a promising therapeutic agent for treating non-alcoholic fatty liver disease. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/#myprospero), identifier (CRD42022335822).