Relationship Between Growth Mindset and Self-Control Amongst Chinese Primary School Students: A Longitudinal Study.

Purpose: Growth mindset and self-control, both recognized as pivotal qualities with significant impacts on personal success, possess respective robust predictive power for academic achievement and broader life outcomes. However, the bidirectional relationship between them remains largely unexplored. This study aims to investigate whether growth mindset, conceptualized as the belief that abilities can be developed through effort and support, prospectively predicts the development of self-control over time. Additionally, it endeavors to explore whether self-control, a crucial positive psychological trait, exerts an influence on the fostering of growth mindset. In summary, our research focuses on elucidating the bidirectional relationship between growth mindset and self-control among Chinese primary school students. Participants and Methods: The current research recruited a sample of 428 primary school students, aged 9-12, from China (214 females, mean age = 9.64 ± 1.21) to participate in a longitudinal study. Participants underwent two follow-up assessments of growth mindset and self-control over a six-month period. Results: The correlation analysis revealed significant associations between growth mindset at T1 and self-control at T2, as well as between self-control at T1 and growth mindset at T2(r = 0.23 to 0.25, ps < 0.01). Cross-lagged analysis found that growth mindset at T1 positively predicted self-control at T2 (ß = 0.11, p = 0.04), while self-control at T1 did not significantly predict growth mindset at T2. Conclusion: The results suggest that growth mindset exerts a direct impact on self-control among primary school students. This finding extends the scope of research concerning growth mindset and provides important theoretical inspiration and practical guidance for educators, parents and counselling professionals in assisting students to enhance self-control.

Design, synthesis, and biological evaluation of imidazolylacetophenone oxime derivatives as novel brain-penetrant agents for Alzheimer's disease treatment.

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC50 value of 0.49 µM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aß42 aggregation. Moreover, the selected nuclide [18F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment.

Innovative insights into the enzymatic hydrolysis of salmon milt: Structural and functional analysis influenced by protease type and enzymolysis time.

In this study, hydrolysates were obtained from salmon milts using four proteases (neutrase, papain, trypsin and novozym 11028). The effects of protease type and enzymolysis time (30, 60, 90, and 120 min) on the structural characteristics and functional properties of the hydrolysates were assessed. The fluorescence intensity of all hydrolysates increased as the extension of enzymolysis time, accompanied by an increase in solubility, emulsifying and foaming ability. Trypsin-hydrolysates showed the highest protein recovery and degree of hydrolysis (DH). The electrophoresis indicated that papain-hydrolysates contained more aggregates (>60 kDa), which was confirmed by larger particle size and lower DH. Neutrase-hydrolysate exhibited the smallest particle size and the highest emulsifying and foaming ability, while the highest emulsifying stability appeared in papain-hydrolysates. Neutrase-hydrolysate displayed the strongest antioxidant potential while papain-hydrolysate possessed the weakest. Results demonstrated that the salmon milt protein hydrolysates can be utilized as nutraceutical and functional food ingredients.

Mechanisms of traditional Chinese medicine in the treatment and prevention of gastric cancer.

BACKGROUND: Gastric cancer (GC) ranks as the fifth most prevalent malignancy worldwide. Conventional treatments, including radiotherapy and chemotherapy, often induce severe side effects and significant adverse reactions, and they may also result in drug resistance. Consequently, there is a critical need for the development of new therapeutic agents. Traditional Chinese Medicine (TCM) and natural products are being extensively researched due to their low toxicity, multi-targeted approaches, and diverse pathways. Scholars are increasingly focusing on identifying active anticancer components within TCM. PURPOSE: This review aims to summarise research conducted over the past 14 years on the treatment of GC using TCM. The focus is on therapeutic targets, mechanisms, and efficacy of Chinese medicine and natural products, including monomer compounds, extracts or analogues, and active ingredients. METHODS: Relevant articles on TCM and GC were retrieved from PubMed using appropriate keywords. The collected articles were screened and classified according to the types of TCM, with an emphasis on the molecular mechanisms underlying the treatment of GC. RESULTS: The research on TCM indicates that TCM and natural products can effectively inhibit the metastasis, proliferation, and invasion of tumour cells. They can also induce apoptosis, autophagy and improve the chemosensitivity of drug-resistant cells. Additionally, injections derived from Chinese herbal medicine, when used as an adjunct to conventional chemotherapy, can significantly improve the prognosis of GC patients by reducing chemotherapy toxicity. CONCLUSION: This review summarises the progress of TCM treatment of GC over the past 14 years, and discusses its therapeutic application of GC, which proves that TCM is a promising treatment strategy for GC in the future.

Polysaccharide NAP-3 Synergistically Enhances the Efficiency of Metformin in Type 2 Diabetes via Bile Acid/GLP-1 Axis through Gut Microbiota Remodeling.

The polysaccharides of edible mushrooms are excellent phytochemicals for adjuvant treatment of metabolic diseases, but the potential mechanisms of synergistic effects are unclear. In this work, we discovered that NAP-3 enhanced the efficiency of metformin in lipid and glucose metabolism in type 2 diabetic (T2D) mice in a gut microbiome-dependent way. NAP-3 remodeled the intestinal microbial, resulting in the decreased activity of bile salt hydrolases and upregulation of CYP27A1 and CYP7B1 functions in the alternative pathway of bile acid synthesis, which leads to accumulation of the conjugated bile acids in ileum, specifically TßMCA and TUDCA. The accumulated conjugated bile acids either blocked or stimulated the nuclear receptors Farnesoid-X-receptor and TGR5, inducing the release of GLP-1 and ultimately enhanced glucose metabolism in mice. Collectively, our research indicated that edible mushroom polysaccharide NAP-3 may serve as a promising adjunctive oral therapeutic agent for T2D.

Band alignment of one-dimensional transition-metal dichalcogenide heterotubes.

One-dimensional (1D) van der Waals (vdW) heterotubes, where different kinds of 1D nanotubes coaxially nest inside each other, offer a flexible platform for promising applications. The various properties of these 1D heterotubes depend on their diameter. Here, we present a systematic theoretical investigation into the structural and electronic properties of two kinds of 1D transition-metal dichalcogenide (TMD) heterotubes. We demonstrate that the thermodynamic stability of 1D heterotubes is determined by their interlayer distance. Additionally, we establish that the band alignment transition changes from type I to type II in 1D TMD heterotubes. We identify two distinct transition mechanisms, originating from the exchange of either the valence band maximum or the conduction band minimum. According to an electrostatic model, the band alignment transition is attributed to the interlayer electric field effect, which depends on the heterotube diameter. The findings in this work provide valuable physical insights into the band alignment transition in 1D heterotubes and are instrumental for their potential applications in nanotechnology.

Heat Shock Protein 90 Interactome-Mediated Proteolysis Targeting Chimera (HIM-PROTAC) Degrading Glutathione Peroxidase 4 to Trigger Ferroptosis.

Targeted protein degradation (TPD) is an emerging therapeutic paradigm aimed at eliminating the disease-causing protein with aberrant expression. Herein, we report a new approach to inducing intracellular glutathione peroxidase 4 (GPX4) protein degradation to trigger ferroptosis by bridging the target protein to heat shock protein 90 (HSP90), termed HSP90 interactome-mediated proteolysis targeting chimera (HIM-PROTAC). Different series of HIM-PROTACs were synthesized and evaluated, and two of them, GDCNF-2/GDCNF-11 potently induced ferroptosis via HSP90-mediated ubiquitin-proteasomal degradation of GPX4 in HT-1080 cells with DC50 values of 0.18 and 0.08 µM, respectively. In particular, GDCNF-11 showed 15-fold more ferroptosis selectivity over GPX4 inhibitor ML162. Moreover, these two degraders effectively suppress tumor growth in the mice model with relatively low toxicity as compared to the combination therapy of GPX4 and HSP90 inhibitors. In general, this study demonstrated the feasibility of degrading GPX4 via HSP90 interactome, and thus provided a significant complement to existing TPD strategies.

An in vitro study of a combined patient-specific device for safe and accurate insertion of infrazygomatic crest miniscrews.

OBJECTIVES: To develop and assess the efficacy of a novel combined patient-specific device (CPSD) for the accurate and safe insertion of infrazygomatic crest miniscrews in orthodontic procedures. MATERIALS AND METHODS: Twenty-eight miniscrews were placed in the infrazygomatic crest region of 28 cadaver maxillae using the direct manual method (n = 14) or the CPSD (n = 14) based on preset trajectories. The CPSD, designed based on the integration model, included a positioning guide, an insertion guide, and a depth-limiting groove. Deviations in the insertion site, tip location, insertion angle, and biting depth between the preset and real insertion trajectories were calculated to evaluate the accuracy of miniscrew insertion. Classification frequencies of root proximity, sinus penetration depth, and biting depth of the miniscrew after insertion were also calculated to evaluate the safety of miniscrew insertion. RESULTS: Regarding evaluation of accuracy, significant differences were observed in the deviation values of the insertion site, tip location, insertion angle, and biting depth between the CPSD and freehand groups (P = .001, P < .001, P < .001, P = .039, respectively). Regarding evaluation of safety, a significant difference was observed in the classification frequencies of root proximity between the two groups (P = .016). CONCLUSIONS: Compared with manual insertion, CPSD could be a preferred method for safe and accurate insertion of infrazygomatic crest miniscrews for orthodontists.

Ternary Ag3AuS2 Nanocrystals for Thin-Film Solar Cells.

The concept of clean and pollution-free energy development has promoted the rise of environmentally friendly silver-based chalcogenide nanocrystal (NC) solar cells, but currently reported silver-based NCs need complex synthesis processes at high temperatures that may bring zerovalent noble metal impurities for their high redox potentials. In this study, we report a facile synthesis of novel Ag3AuS2 NCs by injecting highly active oleylamine sulfur complexes as sulfur sources into metal precursor solutions at low temperatures of 60 °C. The obtained Ag3AuS2 NCs exhibit broad absorption spectra and high molar extinction coefficients (106 M-1 cm-1). Then, the Ag3AuS2 NCs are applied as the light-absorbing active layer in environmentally friendly thin-film solar cells. By introducing a hybrid mixture of charge acceptors and donors (NCs/P3HT hybrid film) at the interface, the device gains an absorption increment and enhanced charge extraction, achieving a final power conversion efficiency of 3.38%. This work demonstrates the enormous potential of Ag3AuS2 NCs from low-temperature preparation for photovoltaic applications.

Understanding the textural enhancement of low-salt myofibrillar protein gels filled with pea protein pre-emulsions through interfacial behavior: Effects of structural modification and oil phase polarity.

This study investigated the effects of pea protein pre-emulsions containing triglyceride- or diglyceride-oil on the emulsifying and gelling properties of low-salt myofibrillar protein (MP). Pea protein isolates treated with pH12-shifting (PPIpH) or ultrasonication (PPIU) demonstrated superior initial interfacial adsorption and higher final interfacial pressure than native pea protein. Within MP/PPI blends, an increased ratio of MP led to a decrease in interfacial pressure, while simultaneously enhancing film elasticity at both polar and non-polar interfaces. Polar diglyceride promoted protein adsorption and fostered interfacial interactions between modified pea proteins and MP, enhancing the cross-linking of transglutaminase (TG) in the composite emulsion gels. Combining diglyceride-type PPIU and PPIpH emulsions with TG increased gel strength to 0.58 N and 0.63 N, respectively, from an initial 0.33 N, yielding a denser protein network with uniformly dispersed oil droplets. Therefore, the utilization of diglyceride and modified PPI can serve as structural enhancers in comminuted meat products.

Genomic biology and therapeutic strategies of liver metastasis from gastric cancer.

The liver is a frequent site of metastasis in advanced gastric cancer (GC). Despite significant advancements in diagnostic and therapeutic techniques, the overall survival rate for patients afflicted with gastric cancer liver metastasis (GCLM) remains dismally low. Precision oncology has made significant progress in identifying therapeutic targets and enhancing our understanding of metastasis mechanisms through genome sequencing and molecular characterization. Therefore, it is crucial to have a comprehensive understanding of the various molecular processes involved in GCLM and the fundamental principles of systemic therapy to develop new treatment approaches. This paper aims to review recent findings on the diagnosis, potential biomarkers, and therapies targeting the multiple molecular processes of GCLM, with the goal of improving treatment strategies for patients with GCLM.

Effects of biochar and wood vinegar co-application on composting ammonia and nitrous oxide losses and fertility.

Composting faces challenges with nitrogen (N) losses through ammonia (NH3) and nitrous oxide (N2O) emissions. In this study, wood vinegar (WV) and biochar (BC) were applied individually or combined into wheat straw and chicken manure composting. Results showed that BC and WV reduced NH3 volatilizations by 22-23 % individually, but their combined application achieved a 59 % reduction. However, this combination increased N2O emissions by 174 %. The BC + WV treatment improved compost quality, evidenced by increased total N content by 22 % and enhanced the biological index, promoting additional dissolved organic matter production. Overall, BC and WV applications improved compost quality, reduced gaseous N losses, and supported the re-utilization of agricultural residues. The combined use of BC and WV significantly enhances compost quality and reduces NH3 emissions, offering a promising solution for sustainable agricultural residue management.

Effects of exposure length, cortical and trabecular bone contact areas on primary stability of infrazygomatic crest mini-screws at different insertion angles.

BACKGROUND: The infrazygomatic crest mini-screw has been widely used, but the biomechanical performance of mini-screws at different insertion angles is still uncertain. The aim of this study was to analyse the primary stability of infrazygomatic crest mini-screws at different angles and to explore the effects of the exposure length (EL), screw-cortical bone contact area (SCA), and screw-trabecular bone contact area (STA) on this primary stability. METHODS: Ninety synthetic bones were assigned to nine groups to insert mini-screws at the cross-combined angles in the occlusogingival and mesiodistal directions. SCA, STA, EL, and lateral pull-out strength (LPS) were measured, and their relationships were analysed. Twelve mini-screws were then inserted at the optimal and poor angulations into the maxillae from six fresh cadaver heads, and the same biomechanical metrics were measured for validation. RESULTS: In the synthetic-bone test, the LPS, SCA, STA, and EL had significant correlations with the angle in the occlusogingival direction (rLPS = 0.886, rSCA = -0.946, rSTA = 0.911, and rEL= -0.731; all P < 0.001). In the cadaver-validation test, significant differences were noted in the LPS (P = 0.011), SCA (P = 0.020), STA (P = 0.004), and EL (P = 0.001) between the poor and optimal angulations in the occlusogingival direction. The STA had positive correlations with LPS (rs = 0.245 [synthetic-bone test] and r = 0.720 [cadaver-validation test]; both P < 0.05). CONCLUSIONS: The primary stability of the infrazygomatic crest mini-screw was correlated with occlusogingival angulations. The STA significantly affected the primary stability of the infrazygomatic crest mini-screw, but the SCA and EL did not.

Introduction of broadleaf tree species can promote the resource use efficiency and gross primary productivity of pure forests.

Long-term pure forest (PF) management and successive planting has result resulted in "low-efficiency artificial forests" in large areas. However, controversy persists over the promoting effect of introduction of broadleaf tree species on production efficiency of PF. This study hypothesised that introduced broadleaf tree species can significantly promote both water-nutrient use efficiency and gross primary productivity (GPP)of PF. Tree ring chronologies, water source, water use efficiency and GPP were analysed in coniferous Cunninghamia lanceolata and broadleaved Phoebe zhennan growing over the past three decades. The introduction of P. zhennan into C. lanceolata plantations resulted in inter-specific competition for water, probably because of the similarity of the main water source of these two tree species. However, C. lanceolata absorbed more water with a higher nutrient level from the 40-60-cm soil layer in mixed forests (MF). Although the co-existing tree species limited the basal area increment and growth rates of C. lanceolata in MF plots, the acquisition of dissolved nutrients from the fertile topsoil layer were enhanced; this increased the water use efficiency and GPP of MF plots. To achieve better ecological benefits and GPP, MFs should be constructed in southern China.

NDRG1 enhances the sensitivity to Cetuximab by promoting Stat1 ubiquitylation in colorectal cancer.

INTRODUCTION: Cetuximab (CTX) is an effective targeted drug for the treatment of metastatic colorectal cancer, but it is effective only in patients with wild-type KRAS genes. Even in this subset of patients, the sensitivity of CTX in patients with right hemi-colon cancer is much lower than that in patients with left hemi-colon cancer. This significantly limits its clinical application. Therefore, further elucidation of the underlying molecular mechanisms is needed. N-myc downstream-regulated gene 1 (NDRG1) plays an important role in solid tumor invasion and metastasis, but whether it can influence CTX sensitivity has not been thoroughly investigated. OBJECTIVE: Our study aimed to identify a novel mechanism by which NDRG1 affects CTX sensitivity. METHODS: Through mass spectrometry analysis of our previously constructed CTX-resistant RKO and HCT116 cells, we found that the signal transducer and activator of transcription-1 (Stat1) might be a potential target of NDRG1. By knocking out NDRG1 or/and Stat1 genes, we then applied the loss-of-function experiments to explore the regulatory relationship between NDRG1 and Stat1 and their roles in the cell cycle, epithelial-mesenchymal transition (EMT), and the sensitivity to CTX in these two colorectal cancer (CRC) cells. Finally, we used the nude-mouse transplanted tumor model and human CRC samples to verify the expression of NDRG1 and Stat1 and their impact on CTX sensitivity in vivo. RESULTS: Stat1 was upregulated in CTX-resistant cells, whereas NDRG1 was downregulated. Mechanically, NDRG1 was inversely correlated with Stat1 expression. It suppressed CRC cell proliferation, migration, and invasion, and promoted apoptosis and epithelial-mesenchymal transition (EMT) by inhibiting Stat1. In addition, NDRG1 directly interacted with Stat1 and promoted Smurf1-induced Stat1 ubiquitination. Importantly, this novel NDRG1-dependent regulatory loop also enhanced CTX sensitivity both in vitro and in vivo. CONCLUSION: Our study revealed that NDRG1 enhanced the sensitivity to Cetuximab by inhibiting Stat1 expression and promoting its ubiquitination in colorectal cancer, elucidating NDRG1 might be a potential therapeutic target for refractory CTX-resistant CRC tumors. But its clinical value still needs to be validated in a larger sample size as well as a different genetic background.

Intrinsic ultralow lattice thermal conductivity in lead-free halide perovskites Cs3Bi2X9 (X = Br, I).

Lead-free halide perovskites have recently garnered significant attention due to their rich structural diversity and exceptionally ultralow lattice thermal conductivity (κL). Here, we employ first-principles calculations in conjunction with self-consistent phonon theory and Boltzmann transport equations to investigate the crystal structure, electronic structure, mechanical properties, and κLs of two typical vacancy-ordered halide perovskites, denoted with the general formula Cs3Bi2X9 (X = Br, I). Ultralow κLs of 0.401 and 0.262 W mK-1 at 300 K are predicted for Cs3Bi2Br9 and Cs3Bi2I9, respectively. Our findings reveal that the ultralow κLs are mainly associated with the Cs rattling-like motion, vibrations of halide polyhedral frameworks, and strong scattering in the acoustic and low-frequency optical phonon branches. The structural analysis indicates that these phonon dynamic properties are closely relevant to the bonding hierarchy. The presence of the extended Bi-X antibonding states at the valence band maximum contributes to the soft elastic lattice and low phonon group velocities. Compared to Cs3Bi2Br9, the face-sharing feature and weaker bond strength in Cs3Bi2I9 lead to a softer elasticity modulus and stronger anharmonicity. Additionally, we demonstrate the presence of wave-like κC in Cs3Bi2X9 by evaluating the coherent contribution. Our work provides the physical microscopic mechanisms of the wave-like κC in two typical lead-free halide perovskites, which are beneficial to designing intrinsic materials with the feature of ultralow κL.

Atlas of Metastatic Gastric Cancer Links Ferroptosis to Disease Progression and Immunotherapy Response.

BACKGROUND & AIMS: Metastases from gastric adenocarcinoma (GAC) lead to high morbidity and mortality. Developing innovative and effective therapies requires a comprehensive understanding of the tumor and immune biology of advanced GAC. Yet, collecting matched specimens from advanced, treatment-naïve patients with GAC poses a significant challenge, limiting the scope of current research, which has focused predominantly on localized tumors. This gap hinders deeper insight into the metastatic dynamics of GAC. METHODS: We performed in-depth single-cell transcriptome and immune profiling on 68 paired, treatment-naïve, primary metastatic tumors to delineate alterations in cancer cells and their tumor microenvironment during metastatic progression. To validate our observations, we conducted comprehensive functional studies both in vitro and in vivo, using cell lines and multiple patient-derived xenograft and novel mouse models of GAC. RESULTS: Liver and peritoneal metastases exhibited distinct properties in cancer cells and dynamics of tumor microenvironment phenotypes, supporting the notion that cancer cells and their local tumor microenvironments co-evolve at metastatic sites. Our study also revealed differential activation of cancer meta-programs across metastases. We observed evasion of cancer cell ferroptosis via GPX4 up-regulation during GAC progression. Conditional depletion of Gpx4 or pharmacologic inhibition of ferroptosis resistance significantly attenuated tumor growth and metastatic progression. In addition, ferroptosis-resensitizing treatments augmented the efficacy of chimeric antigen receptor T-cell therapy. CONCLUSIONS: This study represents the largest single-cell dataset of metastatic GACs to date. High-resolution mapping of the molecular and cellular dynamics of GAC metastasis has revealed a rationale for targeting ferroptosis defense in combination with chimeric antigen receptor T-cell therapy as a novel therapeutic strategy with potential immense clinical implications.

A new neuroprotective candidate TJ1 targeting amyloidogenesis in 5xFAD Alzheimer's disease mice.

As one of the main pathmechanisms of Alzheimer's disease (AD), amyloid-ß (Aß) is widely considered to be the prime target for the development of AD therapy. Recently, imidazolylacetophenone oxime ethers or esters (IOEs) have shown neuroprotective effects against neuronal cells damage, suggesting their potential use in the prevention and treatment of AD. Thirty IOEs compounds from our lab in-house library were constructed and screened for the inhibitory effects on Aß42-induced cytotoxicity. Among them, TJ1, as a new IOEs hit, preliminarily showed the effect on inhibiting Aß42-induced cytotoxicity. Furthermore, the inhibitory effects of TJ1 on Aß42 aggregation were tested by ThT assays and TEM. The neuroprotective effects of TJ1 were evaluated in Aß42-stimulated SH-SY5Y cells, LPS-stimulated BV-2 cells, and H2O2- and RSL3-stimulated PC12 cells. The cognitive improvement of TJ1 was assessed in 5xFAD (C57BL/6J) transgenic mouse. These results showed that TJ1 had strong neuroprotective effects and high blood-brain barrier (BBB) permeability without obvious cytotoxicity. TJ1 impeded the self-accumulation process of Aß42 by acting on Aß oligomerization and fibrilization. Besides, TJ1 reversed Aß-, H2O2- and RSL3-induced neuronal cell damage and decreased neuroinflammation. In 5xFAD mice, TJ1 improved cognitive impairment, increased GSH level, reduced the level of Aß42 and Aß plaques, and attenuated the glia reactivation and inflammatory response in the brain,. Taken together, our results demonstrate that TJ1 improves cognitive impairments as a new neuroprotective candidate via targeting amyloidogenesis, which suggests the potential of TJ1 as a treatment for AD.

Prediction of tumor regression grade in far-advanced gastric cancer after preoperative immuno-chemotherapy using dual-energy CT-derived extracellular volume fraction.

OBJECTIVES: This study examines the effectiveness of dual-energy CT (DECT) delayed-phase extracellular volume (ECV) fraction in predicting tumor regression grade (TRG) in far-advanced gastric cancer (FAGC) patients receiving preoperative immuno-chemotherapy. MATERIALS AND METHODS: A retrospective analysis was performed on far-advanced gastric adenocarcinoma patients treated with preoperative immuno-chemotherapy at our institution from August 2019 to March 2023. Patients were categorized based on their TRG into pathological complete response (pCR) and non-pCR groups. ECV was determined using the delayed-phase iodine maps. In addition, tumor iodine densities and standardized iodine ratios were meticulously analyzed using the triple-phase enhanced iodine maps. Univariate analysis with five-fold cross-validation and Spearman correlation determined DECT parameters and clinical indicators association with pCR. The predictive accuracy of these parameters for pCR was evaluated using a weighted logistic regression model with five-fold cross-validation. RESULTS: Of the 88 patients enrolled (mean age 60.8 ± 11.1 years, 63 males), 21 (23.9%) achieved pCR. Univariate analysis indicated ECV's significant role in differentiating between pCR and non-pCR groups (average p value = 0.021). In the logistic regression model, ECV independently predicted pCR with an average odds ratio of 0.911 (95% confidence interval, 0.798-0.994). The model, incorporating ECV, tumor area, and IDAV (the relative change rate of iodine density from venous phase to arterial phase), showed an average area under curves (AUCs) of 0.780 (0.770-0.791) and 0.766 (0.731-0.800) for the training and validation sets, respectively, in predicting pCR. CONCLUSION: DECT-derived ECV fraction is a valuable predictor of TRG in FAGC patients undergoing preoperative immuno-chemotherapy. CLINICAL RELEVANCE STATEMENT: This study demonstrates that DECT-derived extracellular volume fraction is a reliable predictor for pathological complete response in far-advanced gastric cancer patients receiving preoperative immuno-chemotherapy, offering a noninvasive tool for identifying potential treatment beneficiaries.

5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer's disease mice model.

Alzheimer's disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC50 of 6.2 µM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood-brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile.