Phyllanthus emblica Fruit Improves Obesity by Reducing Appetite and Enhancing Mucosal Homeostasis via the Gut Microbiota-Brain-Liver Axis in HFD-Induced Leptin-Resistant Rats.

The impact of leptin resistance on intestinal mucosal barrier integrity, appetite regulation, and hepatic lipid metabolism through the microbiota-gut-brain-liver axis has yet to be determined. Water extract of Phyllanthus emblica L. fruit (WEPE) and its bioactive compound gallic acid (GA) effectively alleviated methylglyoxal (MG)-triggered leptin resistance in vitro. Therefore, this study investigated how WEPE and GA intervention relieve leptin resistance-associated dysfunction in the intestinal mucosa, appetite, and lipid accumulation through the microbiota-gut-brain-liver axis in high-fat diet (HFD)-fed rats. The results showed that WEPE and GA significantly reduced tissues (jejunum, brain, and liver) MG-evoked leptin resistance, malondialdehyde (MDA), proinflammatory cytokines, SOCS3, orexigenic neuropeptides, and lipid accumulation through increasing leptin receptor, tight junction proteins, antimicrobial peptides, anorexigenic neuropeptides, excretion of fecal triglyceride (TG), and short-chain fatty acids (SCFAs) via a positive correlation with the Allobaculum and Bifidobacterium microbiota. These novel findings suggest that WEPE holds the potential as a functional food ingredient for alleviating obesity and its complications.

DFUSNN: zero-shot dual-domain fusion unsupervised neural network for parallel MRI reconstruction.

Objective. Recently, deep learning models have been used to reconstruct parallel magnetic resonance (MR) images from undersampled k-space data. However, most existing approaches depend on large databases of fully sampled MR data for training, which can be challenging or sometimes infeasible to acquire in certain scenarios. The goal is to develop an effective alternative for improved reconstruction quality that does not rely on external training datasets.Approach. We introduce a novel zero-shot dual-domain fusion unsupervised neural network (DFUSNN) for parallel MR imaging reconstruction without any external training datasets. We employ the Noise2Noise (N2N) network for the reconstruction in the k-space domain, integrate phase and coil sensitivity smoothness priors into the k-space N2N network, and use an early stopping criterion to prevent overfitting. Additionally, we propose a dual-domain fusion method based on Bayesian optimization to enhance reconstruction quality efficiently.Results. Simulation experiments conducted on three datasets with different undersampling patterns showed that the DFUSNN outperforms all other competing unsupervised methods and the one-shot Hankel-k-space generative model (HKGM). The DFUSNN also achieves comparable results to the supervised Deep-SLR method.Significance. The novel DFUSNN model offers a viable solution for reconstructing high-quality MR images without the need for external training datasets, thereby overcoming a major hurdle in scenarios where acquiring fully sampled MR data is difficult.

Effect of Indian gooseberry extract on improving methylglyoxal-associated leptin resistance in peripheral tissues of high-fat diet-fed rats.

Increased leptin resistance and methylglyoxal (MG) levels are observed in obese patients. However, whether MG deposits contribute to leptin resistance, oxidative stress, and inflammation in peripheral tissues remains unclear. In addition, the edible fruit of Indian gooseberry (Phyllanthus emblica L.) contains abundant bioactive components such as vitamin C, ß-glucogallin (ß-glu), gallic acid (GA), and ellagic acid (EA). Water extract of Indian gooseberry fruit (WEIG) and GA has been shown to improve cognitive decline by suppressing brain MG-induced insulin resistance in rats administered a high-fat diet (HFD). Accordingly, this study investigated the functions of WEIG and GA in inhibiting MG-induced leptin resistance, oxidative stress, and inflammation in the peripheral tissues of HFD-fed rats. The results showed that MG, advanced glycation end products (AGEs), and leptin resistance accumulation in the liver, kidney, and perinephric fat were effectively restored by elevated glyoxalase-1 (Glo-1) activity after WEIG and GA administration comparable to that of alagebrium chloride (positive control) treatment in HFD-fed rats. Furthermore, WEIG and GA supplementation increased adiponectin and antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase) and decreased inflammatory cytokines (IL-6, IL-1ß, TNF-α) in the peripheral tissues of HFD-fed rats. In conclusion, these findings demonstrated that MG may trigger leptin resistance, oxidative stress, and inflammation in peripheral tissues, which could be abolished by WEIG and GA treatment. These results show the potential of P. emblica for functional food development and improving obesity-associated metabolic disorders.

Pterostilbene and 6-shogaol exhibit inhibitory effects on sunitinib resistance and motility by suppressing the RLIP76-initiated Ras/ERK and Akt/mTOR pathways in renal cancer cells.

Sunitinib (SUN) is the first-line targeted therapeutic drug for advanced renal cell carcinoma (RCC). However, SUN resistance is frequently observed to result in tumor metastasis, with a poor survival rate. Therefore, finding an effective and safe adjuvant to reduce drug resistance is important for RCC treatment. Pterostilbene (PTE) and 6-shogaol (6-S) are natural phytochemicals found in edible sources and have potential applications against various cancers. However, the biological mechanisms of PTE and 6-S in SUN-resistant RCC are still unclear. Accordingly, this study investigated the regulatory effects of PTE and 6-S on cell survival, drug resistance, and cell invasion in 786-O and SUN-resistant 786-O (786-O SUNR) cells, respectively. The results demonstrated that PTE and 6-S induced apoptosis in both cell lines by upregulating the Bax/Bcl-2 ratio. Additionally, PTE and 6-S increased SUN sensitivity by inhibiting the expression of the RLIP76 transport protein, reduced cell invasion and downregulated MMP expression in both 786-O and 786-O SUNR cells. Mechanistically, PTE, and 6-S significantly and dose-dependently suppressed the RLIP76-initiated Ras/ERK and Akt/mTOR pathways. In summary, PTE and 6-S induce apoptosis, enhance SUN sensitivity, and inhibit migration in both 786-O and 786-O SUNR cells. These novel findings demonstrate the potential of PTE and 6-S as target therapeutic adjuvants for RCC treatment.

circ-Amotl1 in extracellular vesicles derived from ADSCs improves wound healing by upregulating SPARC translation.

Aim: This study aims to explore the mechanism of circ- AMOT-like protein 1 (Amotl1) in extracellular vesicles (Evs) derived from adipose-derived stromal cells (ADSCs) regulating SPARC translation in wound healing process. Methods: The morphology, wound healing rate of the wounds and Ki67 positive rate in mouse wound healing models were assessed by H&E staining and immunohistochemistry (IHC). The binding of IGF2BP2 and SPARC was verified by RNA pull-down. Adipose-derived stromal cells (ADSCs) were isolated and verified. The Evs from ADSCs (ADSC-Evs) were analyzed. Results: Overexpression of SPARC can promote the wound healing process in mouse models. IGF2BP2 can elevate SPARC expression to promote the proliferation and migration of HSFs. circ-Amotl1 in ADSC-Evs can increase SPARC expression by binding IGF2BP2 to promote the proliferation and migration of HSFs. Conclusion: ADSC-Evs derived circ-Amotl1 can bind IGF2BP2 to increase SPARC expression and further promote wound healing process.

Phyllanthus emblica L. polysaccharides ameliorate colitis via microbiota modulation and dual inhibition of the RAGE/NF-κB and MAPKs signaling pathways in rats.

Pharmacological treatments for colitis have limited efficacy and side effects. Plant polysaccharides improve colitis by modulating the gut microbiota. However, the specific benefits of Phyllanthus emblica L. polysaccharides (PEPs) in colitis remain unclear. Therefore, this study aimed to assess the physical characteristics and health advantages of PEP in rats subjected to 2,4,6-trinitrobenzene sulfonic acid (TNBS) treatment. The results showed that PEP (1.226 × 103 kDa) was an α-acidic pyran heteropolysaccharide rich in galactose and galacturonic acid. Prefeeding rats with PEP significantly decreased the levels of NO, MDA, proinflammatory cytokines (IL-6, IL-1ß, TNF-α), apoptosis, and the activities of mucinase and ß-glucuronidase. These changes were accompanied by increases in the levels of anti-inflammatory cytokines (IL-4, IL-10) and antioxidant enzymes (SOD, catalase, GPx) in colitis rats. Mechanistically, PEP suppressed the abundance of inflammatory-related bacteria (Bacteroides, Intestinimonas, and Parabacteroides) while promoting the growth of short-chain fatty acid (SCFA)-producing bacteria (Romboutsia, Clostridium_sensu_stricto_1, and Lactobacillus), along with an increase in SCFA secretion. SCFAs may engage with the GPR43 receptor and inhibit downstream HDAC3, consequently downregulating the activation of the RAGE/NF-κB and MAPK pathways. In conclusion, PEP demonstrated preventive effects through its antioxidant, anti-inflammatory, and microbiota modulation properties, thereby ameliorating TNBS-induced colitis in rats.

Design and verification of a high-gradient and high-power 2nd harmonic cavity for the China Spallation Neutron Source upgrade project.

Here, we report our recent progress in the design, fluid thermodynamics simulation, and high-power test of the2nd harmonic cavity for the China Spallation Neutron Source Phase II. A high-performance and large-size magnetic alloy (MA) core was developed as the load material for the radiofrequency cavity to achieve a high gradient of 40 kV/m. The water-cooling structure and cooling efficiency were studied and improved through numerical analysis and thermal experiments. The long-term stability of the cavity, especially the waterproofness of the MA cores with high heat load, was verified by high power tests.

A low-frequency normal conducting cavity with higher-order mode damping for fourth-generation synchrotron radiation sources.

The utilization of a low-frequency (<200 MHz) RF system in storage facilitates the attainment of ultra-low emittances in synchrotron light sources through on-axis injection. This paper focuses on the development of a low-frequency normal conducting (NC) cavity with higher-order mode (HOM) damping for fourth-generation synchrotron light sources. We propose a novel approach to achieve efficient HOM damping in a NC cavity by optimizing the lowest frequency HOM and implementing a beam-line absorber. Notably, unlike conventional NC cavities, the presence of a large beam tube for the beam-line absorber does not compromise the accelerating performance in a coaxial resonant cavity, enabling effective HOM damping while maintaining a high shunt impedance. Through simulations, the prototype design of a 166.6 MHz HOM-damped cavity demonstrates a fundamental mode impedance of ∼8 MΩ, with longitudinal and transverse HOM impedances below 2.0 and 50 kΩ/m, respectively.

Reflection power suppression for solid state amplifiers with combiner optimization.

The application of high-power solid state amplifiers (SSAs) in accelerator facilities is increasing, and equipment failure caused by reflected power is the main risk to their long-term operation. High-power SSAs often comprise multiple power amplifier modules. Full power reflection is more likely to damage the modules in SSAs if the amplitudes of the modules are unequal. Optimization of the power combiners is an effective means for improving the stability of SSAs under high power reflection. This study analyzes the mechanisms and conditions of reflected power generation using the scattering parameters of the combiner and proposes an optimization scheme for the combiner. The simulation and experimental results show that some modules may receive reflected power as high as nearly four times the rated power of one module when the SSA meets certain conditions, which could damage the modules. The maximum reflected power can be effectively reduced and the anti-reflection ability of SSAs can be improved by optimizing the combiner parameters to suppress the maximum reflected power.

Protective effect of rosmarinic acid-rich extract from Trichodesma khasianum Clarke against microbiota dysbiosis in high-fat diet-fed obese mice.

Hypertrophy of adipose tissues and dysbiosis are hallmarks of obesity. Although drugs are applied for obesity treatment, side effects limit their use. The anti-obesity capacity of rosmarinic acid (RA) has been documented. Trichodesma khasianum Clarke is an edible RA-rich plant grown in Taiwan. Our previous study found that an 80 % ethanol extract of T. khasianum Clarke leaves (80EETC) ameliorates gastric mucosal damage through its anti-inflammatory, antioxidant, and microbiota modulation abilities. However, the anti-obesity effect of 80EETC remains unclear. Therefore, the objective of this study was to explore the protective effects of low-dose 80EETC (125 mg/kg b.w., 80EETCL) or high-dose 80EETC (250 mg/kg b.w., 80EETCH) on obesity development through gut microbiota modulation in high-fat diet (HFD)-induced C57BL/6 mice. The results showed a high RA content (89.2 ± 7.4 mg/g) in 80EETC. 80EETC administration significantly decreased body weight, body fat ratio, serum lipid levels (TC, TG, and LDL-C), adipose tissue accumulation, malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in HFD-fed mice. Furthermore, supplementation with 80EETC reduced the Firmicutes/Bacteroidetes ratio and enhanced the relative abundance of gut microbiota (p_Bacteroidetes, f_Lactobacillus, f_Muribaculaceae, f_Prevotellaceae, g_Lactobacillus, g_Prevotellaceae_NK3B31_group, g_Ruminococcaceae_UCG-013, and g_Ruminococcaceae_UCG-014), which negatively correlated with obesity-related factors such as body weight, energy intake, fat accumulation in adipose tissue, TC, TG, LDL, and MDA. In conclusion, RA-rich 80EETC had a protective effect against obesity development and it has potential in healthy food applications.

Preventive Effect of Indian Gooseberry (Phyllanthus emblica L.) Fruit Extract on Cognitive Decline in High-Fat Diet (HFD)-Fed Rats.

SCOPE: Methylglyoxal (MG)-derived advanced glycation end products (AGEs) directly bind to the receptor for advanced glycation end products (RAGE), subsequently exacerbating obesity and obesity-induced cognitive decline. Indian gooseberry (Phyllanthus emblica L.) fruit has antiobesity properties. However, the underlying mechanism by which Indian gooseberry fruit prevents obesity-induced cognitive decline remains unclear. METHODS AND RESULTS: This study aims to investigate the preventive effect of a water extract of Indian gooseberry fruit (WEIG) and its bioactive compound gallic acid (GA) on the obesity-induced cognitive decline through MG suppression and gut microbiota modulation in high-fat diet (HFD)-fed rats. Trapping MG, WEIG, and GA significantly ameliorate fat accumulation in adipose tissue and learning and memory deficits. Mechanistically, WEIG and GA administration effectively reduces brain MG and AGE levels and subsequently reduces insulin resistance, inflammatory cytokines, MDA production, and Alzheimer's disease-related proteins, but increases both antioxidant enzyme activities and anti-inflammatory cytokine with inhibiting RAGE, MAPK, and NF-κB levels in HFD-fed rats. Additionally, WEIG and GA supplementation increases the relative abundances of Bacteroidetes, Gammaproteobacteria, and Parasutterella, which negatively correlate with MG, inflammatory cytokine, and Alzheimer's disease-related protein expressions. CONCLUSION: This novel finding provides a possible mechanism by which WEIG prevents obesity-induced cognitive decline through the gut-brain axis.

Ameliorative effect of buckwheat polysaccharides on colitis via regulation of the gut microbiota.

Plant polysaccharides act as prebiotics by modulating gut microbiota. However, the functional characteristics of buckwheat Fagopyrum tataricum polysaccharides (FTP) and F. esculentum polysaccharides (FEP) on colitis prevention are not valid. This study evaluated the ameliorative effects of FTP and FEP against TNBS-induced colitis via gut microbiota modulation in rats. The characterizations of FTP and FEP were analyzed, including FTIR, TGA, DSC, and monosaccharide composition. In addition, the pathological features of colon length and symptoms in TNBS-induced colitis were improved via the intragastric preadministration of FTP and FEP. The results showed that prefeeding with FTP and FEP decreased inflammatory cytokines (IL-6, IL-1ß, and TNF-α), ß-glucuronidase, and mucinase, as well as increasing superoxide dismutase, catalase, and glutathione peroxidase levels, in TNBS-induced rats. A decrease in inflammatory signaling-associated proteins (NF-κB, MAPK, COX-2, and iNOS) improved the treatment of TNBS-induced colitis by buckwheat polysaccharides. Moreover, prefeeding with buckwheat polysaccharides increased the Firmicutes/Bacteroidetes ratio and short-chain fatty acid (SCFA) production and decreased the abundance of inflammation-related bacteria (Oscillospiraceae and Oscillibacter). In conclusion, FTP and FEP strongly improved TNBS-induced colitis through antioxidant, anti-inflammatory, and microbiota modulation properties, especially in the high-dose FEP group. Buckwheat polysaccharides have the potential for utilization in functional ingredients or food development.

Rhinacanthus nasutus and okara polysaccharides attenuate colitis via inhibiting inflammation and modulating the gut microbiota.

Plant polysaccharides have prebiotic properties for gut microbiota and immune modulation. This study aimed to investigate the prevention abilities of edible Rhinacanthus nasutus polysaccharide (RNP) and okara polysaccharide (OP) in Sprague-Dawley rats with acetic acid-induced colitis. The characterizations of RNP and OP were analyzed, including Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, and monosaccharide composition. The prebiotic properties of RNP and OP were determined in vitro. In addition, the pathological features of colon length and inflammatory cytokine levels in acetic acid-induced colitis were improved by intragastric preadministration of RNP and OP for 3 weeks. There was no nephrotoxicity or hepatotoxicity in rats via histopathological assessment after RNP and OP intake. Moreover, the abundance of short-chain fatty acids-producing bacteria (Lachnospiraceae, Lactobacilli, and Prevotellaceae) were increased after RNP supplementation. In conclusion, intragastric gavage of RNP and OP significantly modulated the gut microbiota and immune response, consequently alleviating the symptoms of colitis. This novel finding provides an alternative strategy and potential application of these two polysaccharides for colitis prevention and treatment.

Linker engineering in metal-organic frameworks for dark photocatalysis.

Dark reactions featuring continuous activity under light off conditions play a critical role in natural photosynthesis. However, most artificial photocatalysts are inactive upon the removal of the light source, and the artificial photocatalysts with dark photocatalysis abilities have been rarely explored. Herein, we report a Ti-based metal-organic framework (MOF), MIL-125, exhibiting the capability of dark photocatalytic hydrogen production. Remarkably, the introduction of different functional groups onto the linkers enables distinctly different activities of the resulting MOFs (MIL-125-X, X = NH2, NO2, Br). Dynamic and thermodynamic investigations indicate that the production and lifetime of the Ti3+ intermediate are the key factors, due to the electron-donating/-withdrawing effect of the functional groups. As far as we know, this is the first report on dark photocatalysis over MOFs, providing new insights into the storage of irradiation energy and demonstrating their great potential in dark photocatalysis due to the great MOF diversity.

Protective effects of camellia and olive oils against cognitive impairment via gut microbiota-brain communication in rats.

Food intake influences neurofunction via the gut microbiota-brain axis. Monounsaturated fatty acid (MUFA) consumption is highly associated with neuroprotection; the mechanism behind the effects of olive oil and camellia oil on gut microbiota remains unclear. In this study, the objective was to compare the neuroprotective role of oleic acid-rich camellia oil and olive oil against AlCl3-induced mild cognitive impairment (MCI) in rats. Morris water maze tests revealed that learning and memory capacities improved in AlCl3-induced rats subjected to camellia oil administration better than olive oil treatment. Moreover, the results showed that the camellia oil- and olive oil-treated AlCl3-induced rat groups had significantly reduced oxidative stress and inflammatory cytokines. Notably, Spearman correlation analysis indicated that the inflammatory cytokines negatively correlated with the microbial strains (Bacteroides pectinophilus_group and Blautia) in response to camellia oil administration. Furthermore, Ruminococcaceae_UCG014 abundance was significantly enhanced by camellia oil intake, which was highly positively associated with antioxidant activity expression. In conclusion, the novel data suggest that the outcomes of camellia oil consumption were superior to those of olive oil intake as camellia oil may have a beneficial effect on MCI protection and improvement through the gut microbiota-brain communication.

Protective effect of fermented okara on the regulation of inflammation, the gut microbiota, and SCFAs production in rats with TNBS-induced colitis.

Dysbiosis of gut microbiota is intimately related to ulcerative colitis. The literature has revealed the gut microbiota metabolism of dietary fiber, which is a key resource for short-chain fatty acids (SCFAs) production and subsequently leads to anti-inflammatory effects. It is known that okara (a soybean byproduct) is rich in dietary fiber, but the effect of fermented okara on relieving colitis remains unclear. The object of this study was to investigate the effects of Aspergillus oryzae-fermented okara (FO) on colitis prevention through gut microbiota manipulation in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model. The results showed that administration of FO elevated the relative abundance of SCFAs-producing bacteria (Lachnospiraceae and Bifidobacteriaceae) and SCFAs production, which engaged with GPR43 (SCFAs receptor) consequently decreased the production of proinflammatory cytokines (IL-6, IL-1ß, and TNF-α), inflammatory mediators (COX-2, iNOS, PGE2, and NO), and MCP-1 chemokine and increased anti-inflammatory cytokine (IL-10 and IL-4) production through inhibition of HDAC3/MAPK-related proteins and the NF-κB inflammatory pathway in TNBS-induced colitis in rats. Moreover, increased activity of antioxidants, such as SOD, CAT, GSH, and GPx, and decreased MDA and MPO production were also observed after FO administration in TNBS-induced colitis in rats. This study demonstrated the novel potential of soybean byproducts for alleviating TNBS-induced intestinal inflammation and enhancing antioxidant capacity for colitis improvement. This new finding may enhance the value of okara for functional food development.

4-Acetylantroquinonol B enhances cell death and inhibits autophagy by downregulating the PI3K/Akt/MDR1 pathway in gemcitabine-resistant pancreatic cancer cells.

Gemcitabine (GEM) is a typical chemotherapeutic drug used to treat pancreatic cancer, but GEM resistance develops within weeks after chemotherapy. Hence, the development of a new strategy to overcome drug resistance is urgent. 4-Acetylantroquinonol B (4-AAQB), a ubiquinone derived from Taiwanofungus camphoratus, has hepatoprotective, anti-obesity, and antitumor activities. However, the role of 4-AAQB in enhancing GEM sensitivity is unclear. This study aimed to determine the underlying mechanisms by which 4-AAQB enhances cytotoxicity and GEM sensitivity. Cell viability was dramatically reduced by 4-AAQB (2 and 5 µM) treatment in the MiaPaCa-2 and GEM-resistant MiaPaCa-2 (MiaPaCa-2GEMR) human pancreatic cancer cells. 4-AAQB led to cell cycle arrest, upregulated the levels of reactive oxygen species (ROS), promoted apoptosis, and inhibited autophagy, which subsequently enhanced GEM chemosensitivity by suppressing the receptor for advanced glycation end products (RAGE)/high mobility group box 1 (HMGB1)-initiated PI3K/Akt/multidrug resistance protein 1 (MDR1) signaling pathway in both cell lines. Vascular endothelial growth factor A (VEGFA) expression, cell migration, and invasion were also inhibited by the 4-AAQB incubation. Overall, this combination treatment strategy might represent a novel approach for GEM-resistant pancreatic cancer.

A descriptor for the structural stability of organic-inorganic hybrid perovskites based on binding mechanism in electronic structure.

The poor stability of organic-inorganic hybrid perovskites hinders its commercial application, which motivates a need for greater theoretical insight into its binding mechanism. To date, the binding mode of organic cation and anion inside organic-inorganic hybrid perovskites is still unclear and even contradictory. Therefore, in this work based on density functional theory (DFT), the binding mechanism between organic cation and anion was systematically investigated through electronic structure analysis including an examination of the electronic localization function (ELF), electron density difference (EDD), reduced density gradient (RDG), and energy decomposition analysis (EDA). The binding strength is mainly determined by Coulomb effect and orbital polarization. Based on the above analysis, a novel 2D linear regression descriptor that Eb = - 9.75Q2/R0 + 0.00053 V∙EHL - 6.11 with coefficient of determination R2 = 0.88 was proposed to evaluate the binding strength (the units for Q, R0, V, and EHL are |e|, Å, bohr3, and eV, respectively), revealing that larger Coulomb effect (Q2/R0), smaller volume of perovskite (V), and narrower energy difference (EHL) between the lowest unoccupied molecular orbital (LUMO) of organic cation and the highest occupied molecular orbital (HOMO) of anion correspond to the stronger binding strength, which guides the design of highly stable organic-inorganic hybrid perovskites.

Lucidone inhibits autophagy and MDR1 via HMGB1/RAGE/PI3K/Akt signaling pathway in pancreatic cancer cells.

Gemcitabine (GEM) drug resistance remains a difficult challenge in pancreatic ductal adenocarcinoma (PDAC) treatment. Therefore, identifying a safe and effective treatment strategy for PDAC is urgent. Lucidone is a natural compound extracted from the fruits of Lindera erythrocarpa Makino. However, the role of lucidone in PDAC inhibition remains unclear. In addition, high-mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) are involved in multidrug resistance protein 1 (MDR1) regulation and GEM resistance. Thus, this study aimed to explore the function of lucidone in tumor cytotoxicity and chemosensitivity through the suppression of RAGE-initiated signaling in PDAC cells. The data showed that lucidone significantly promoted apoptotic cell death and inhibited the expression of autophagic proteins (Atg5, Beclin-1, LC3-II, and Vps34) and MDR1 by inhibiting the HMGB1/RAGE/PI3K/Akt axis in both MIA Paca-2 cells and MIA Paca-2GEMR cells (GEM-resistant cells). Notably, convincing data were also obtained in experiments involving RAGE-specific siRNA transfection. In addition, remarkable cell proliferation was observed after treatment with lucidone combined with GEM, particularly in MIA Paca-2GEMR cells, indicating that lucidone treatment enhanced chemosensitivity. Collectively, this study provided the underlying mechanism by which lucidone treatment inhibited HMGB1/RAGE-initiated PI3K/Akt/MDR1 signaling and consequently enhanced chemosensitivity in PDAC.

High throughput screening of promising lead-free inorganic halide double perovskites via first-principles calculations.

Perovskite solar cells (PSCs) have been intensively investigated and made great progress due to their high photoelectric conversion efficiency and low production cost. However, poor stability and the toxicity of Pb limit their commercial applications. It is particularly important to search for new non-toxic, high-stability perovskite materials. In this study, 760 Cs2B2+B'2+X6 (X = F, Cl, Br, I) inorganic halide double perovskites are screened based on high-throughput first-principles calculations to obtain an ideal perovskite material. The band gaps of this type of double perovskite are mainly determined by the elements X and B2+, decreasing monotonously with the increase in the atomic number of X (from F to I). We obtain 14 optimal and unreported materials with suitable band gaps as potential alternative materials for Pb-based photovoltaic absorbers in PSCs. This theoretical investigation can provide theoretical guidance for developing novel lead-free PSC materials.