Search Results (1,045)

We recently reported that phospholipase A2 (PLA2)-mediated production of prostaglandins within the ventromedial hypothalamus (VMH) plays a critical role in systemic glucose homeostasis. However, the role of PLA2 in the VMH in regulating food intake is still unclear. Here, we attempted to investigate the role of PLA2 in regulating food intake and body weight in male mice. We injected an adeno-associated virus encoding short hairpin RNA (AAV-shRNA) targeting cytosolic phospholipase A2 (shPla2g4a) into the VMH. We assessed food intake, body weight, oxygen consumption, glucose tolerance, and insulin sensitivity. Three weeks after the AAV injection, the shPla2g4a group exhibited increased food intake and body weight gain compared to controls (shSCRM). Energy expenditure, oxygen consumption, and respiratory quotient (RQ) were comparable between groups. Our findings suggest that the cPLA2-mediated pathway in the VMH is critical for feeding behavior and maintaining energy homeostasis. Further investigation is needed to elucidate the underlying mechanisms. Full article

Background: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair (pMMR) and microsatellite stability (MSS) metastatic colorectal cancer (mCRC). Inhibition of vascular endothelial growth factor (VEGF) or cytotoxic chemotherapy can boost immunogenicity and has the potential to upregulate ICI efficacy. Methods: A comprehensive electronic literature search was conducted up to April 2025 to identify randomized controlled trials comparing cytotoxic chemotherapy plus bevacizumab with or without ICI. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), objective response rate (ORR), and severe adverse events (AEs: grade 3 or more). A meta-analysis was performed using random-effects models to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: Four studies involving 986 patients (With-ICI group, n = 651; Without-ICI group, n = 335) were included. The meta-analysis demonstrated a significant improvement in PFS in the With-ICI group compared with the Without-ICI group, with an HR of 0.82 (95% CI: 0.70–0.96, p = 0.01) without statistical heterogeneity. No significant improvements were observed between the With- and Without-ICI groups in OS and ORR meta-analyses, but the With-ICI group had a favorable trend in OS. A significant increase in serious AEs was not observed in the With-ICI group. Conclusions: This meta-analysis suggests a potential benefit of adding ICIs to chemotherapy plus bevacizumab in pMMR mCRC; however, the evidence remains preliminary and hypothesis-generating, warranting further investigation in biomarker-driven trials and clarification of long-term outcomes. Full article

Salmonella enterica serovar Typhimurium (S. Typhimurium) is an intracellular pathogen capable of surviving and replicating within macrophages, which causes foodborne diseases such as gastroenteritis. To develop a strategy against intracellular bacteria in macrophages, we designed silver-loaded biodegradable polymer nanoparticles functionalized with S. Typhimurium membrane vesicles (MVs). Silver nanoparticles (Ag NPs) were initially encapsulated within biodegradable poly(lactic-co-glycolic) nanoparticles (Ag-P NPs), which were then surface-modified with polyethyleneimine to form Ag-PP NPs. These were subsequently fused with S. Typhimurium MVs via a sonication method to generate Ag-PP@MV NPs. The resulting MV-coated nanoparticles displayed a similar protein profile to that of native MVs and exhibited antibacterial activity against intracellular S. Typhimurium. Notably, the enhanced cellular uptake of the MV-modified NPs contributed to their intracellular bactericidal efficacy. This study highlights MV modification as a promising strategy to improve NP delivery to macrophages for treating persistent intracellular infections. Full article

EGFR is the most frequently altered driver gene in non-small-cell lung cancer (NSCLC), and its overexpression is also associated with breast cancer. In the present study, we synthesized 18 new compounds (B-1, B-2, B-6, B-7, and BP-1–14). The cytotoxicity of these compounds was evaluated in A549 NSCLC and MCF-7 breast cancer cells, as well as in Jurkat cells and PBMCs (healthy). The most potent compounds were further examined for their ability to induce apoptosis in A549 and MCF-7 cells, as well as their EGFR inhibitory activity. Molecular docking was conducted at the ATP-binding site of EGFR, and key pharmacokinetic and toxicity parameters were predicted in silico. B-2 demonstrated the strongest cytotoxicity against A549 and MCF-7 cells (IC₅₀ = 2.14 ± 0.83 μM and 8.91 ± 1.38 μM, respectively), displaying selective cytotoxicity between Jurkat cells and PBMCs (SI = 23.2). B-2 induced apoptosis in A549 and MCF-7 cells at rates of 16.8% and 4.3%, respectively. B-2 inhibited EGFR by 66% at a 10 μM concentration and showed a strong binding affinity to the ATP-binding site of EGFR. Furthermore, B-2 exhibited drug-like characteristics and was not identified as carcinogenic, genotoxic, or mutagenic. B-2 shows promise as an apoptosis inducer and EGFR inhibitor for future anti-NSCLC and anti-breast cancer research. Full article

The present study evaluated the larvicidal and pupicidal activities of pure and mixed monoterpene formulations—eucalyptol, geranial, trans-anethole, and trans-cinnamaldehyde—against Aedes aegypti and compared them with 1% (w/w) temephos. Safety bioassays of all formulations on non-target species confirmed their safety. The combined mixture of eucalyptol + trans-anethole at 400 µg/mL exhibited stronger larvicidal activity, with an LC₅₀ of 176 µg/mL, while the combination of trans-anethole + geranial at 400 µg/mL exhibited stronger pupicidal activity with an LC₅₀ of 167 µg/mL. Both formulations were more effective than a 1% temephos. All the mixture formulations were more strongly synergistic compared to pure formulations, with an increased mortality value (IMV) of 25% to 95%. External morphological aberrations observed at death included swelling of the respiratory system. Importantly, all the formulations were safe for two non-target species: guppies (Poecilia reticulata) and honeybees (Apis mellifera). The combination formulations are strong larvicides and pupicides for controlling Ae. Aegypti, which will help reduce the spread of viruses carried by this vector. Full article

Improved antiretroviral therapy (ART) has significantly increased the life expectancy of people living with HIV (PLWH). At the same time, other complications like metabolic syndrome (MetS) are coming up as new challenges to handle. This review aims to explore the emerging evidence of gut microbiome and virome alterations in human immunodeficiency virus-1 (HIV-1) infection and associated metabolic disorders, such as type-2 diabetes (T2DM) and cardiovascular disease (CVD), with a focus on their interplay, contribution to immune dysfunction, and potential as therapeutic targets. We conducted a comprehensive review of the current literature on gut bacteriome and virome changes in HIV-1-infected individuals and those with metabolic comorbidities emphasizing their complex interplay and potential as biomarkers or therapeutic targets. HIV-1 infection disrupts gut microbial homeostasis, promoting bacterial translocation, systemic inflammation, and metabolic dysregulation. Similarly, metabolic disorders are marked by reduced beneficial short-chain fatty acid-producing bacteria and an increase in pro-inflammatory taxa. Alterations in the gut virome, particularly involving bacteriophages, may exacerbate bacterial dysbiosis and immune dysfunction. Conversely, some viral populations have been associated with immune restoration post-ART. These findings point toward a dynamic and bidirectional relationship between the gut virome, bacteriome, and host immunity. Targeted interventions such as microbiome modulation and fecal virome transplantation (FVT) offer promising avenues for restoring gut homeostasis and improving long-term outcomes in PLWH. Full article

The COVID-19 pandemic severely impacted Japan’s inbound tourism, but recent recovery trends highlight the growing importance of Chinese tourists. Understanding their motivations is crucial for revitalizing the industry. Building on our previous framework, this study applies Transformer-based natural language processing (NLP) models and principal component analysis (PCA) to analyze large-scale user-generated content (UGC) and identify key motivational factors influencing Chinese tourists’ visits to Hokkaido. Traditional survey-based approaches to tourism motivation research often suffer from response biases and small sample sizes. In contrast, we leverage a pre-trained Transformer model, RoBERTa, to score motivational factors like self-expansion, excitement, and cultural observation. PCA is subsequently used to extract the most significant factors across different destinations. Findings indicate that Chinese tourists are primarily drawn to Hokkaido’s natural scenery and cultural experiences, and the differences in these factors by season. While the model effectively aligns with manual scoring, it shows limitations in capturing more abstract motivations such as excitement and self-expansion. This research advances tourism analytics by applying AI-driven methodologies, offering practical insights for destination marketing and management. Future work can extend this approach to other regions and cross-cultural contexts, further enhancing AI’s role in understanding evolving traveler preferences. Full article

Artisanal small-scale gold mining (ASGM) is the largest source of global mercury (Hg) emissions. This study investigated Hg contamination in water, soil, sediment, fish, and cassava plants around ASGM sites in Gunung Pongkor, West Java, Indonesia. Hg concentration ranged from 0.06 to 4.49 µg/L in water; 0.420 to 144 mg/kg dw in soil; 0.920 to 150 mg/kg dw in sediment; 0.259 to 1.23 mg/kg dw in fish; 0.097 to 5.09 mg/kg dw in cassava root; and 0.350 to 8.84 mg/kg dw in cassava leaf. Geo-accumulation index (Igeo) analysis revealed moderate to heavy soil contamination upstream, likely due to direct ASGM input. In contrast, sediment Igeo values indicated heavy contamination downstream, suggesting Hg transport and sedimentation. Bioconcentration factors (BCFs) in fish were predominantly high in downstream and midstream areas, indicating enhanced Hg bioavailability. Bioaccumulation factors (BAFs) in cassava were higher in upstream areas. Health risk assessment, based on the Hazard Quotient (HQ) and Hazard Index (HI), identified ingestion as the primary exposure route, with children exhibiting significantly higher risks than adults. These findings highlight the significant Hg contamination associated with ASGM in Gunung Pongkor and emphasize the need for targeted mitigation strategies to protect human and environmental health. Full article

High-frequency fluctuations in the international crude oil market have led to multilevel characteristics in China’s domestic refined oil pricing mechanism. To address the poor fitting performance of single deep learning models on oil price data, which hampers accurate gasoline price prediction, this paper proposes a gasoline price prediction method based on a combined xLSTM–XGBoost model. Using gasoline price data from June 2000 to November 2024 in Sichuan Province as a sample, the data are decomposed via STL decomposition to extract trend, residual, and seasonal components. The xLSTM model is then employed to predict the trend and seasonal components, while XGBoost predicts the residual component. Finally, the predictions from both models are combined to produce the final forecast. The experimental results demonstrate that the proposed xLSTM–XGBoost model reduces the MAE by 14.8% compared to the second-best sLSTM–XGBoost model and by 83% compared to the traditional LSTM model, significantly enhancing prediction accuracy. Full article

Phased-array ultrasonic transducers using sol–gel composites face challenges in terms of polarization uniformity when using conventional corona poling. Pb(Zr, Ti)O₃ (PZT)/PZT composites with a thickness of 25 µm were fabricated on 3 mm thick titanium substrates, and the samples were poled by AC poling, DC poling, and corona discharge poling at RT. It was found that the polarization direction could be controlled by the voltage off-phase angle. When poling was performed with a voltage off-phase angle of 90°, applied voltage of 200 V (rms), 10 cycles, and frequency of 1 Hz, average values and standards of measured piezoelectric constant d₃₃ of −35.1 ± 0.8 pC/N and ultrasonic sensitivity of 11.4 ± 0.1 dB were obtained. Furthermore, the AC-poled samples demonstrated smaller variations in d₃₃ and ultrasonic sensitivity compared with the corona-poled samples, and higher values of d₃₃ and ultrasonic sensitivity compared with the DC-poled samples, indicating the potential of AC poling for PZT/PZT sol–gel composites with large areas. Full article

Accurate prediction of landslide susceptibility is a key component of disaster risk reduction and early warning systems. Traditional landslide susceptibility prediction methods often face challenges in capturing complex nonlinear and spatio-temporal relationships inherent in geospatial data. In this study, we propose a Convolutional Neural Network (CNN), Long Short-Term Memory (LSTM), Spatial Attention Mechanism (SAM) hybrid deep learning model designed for spatial landslide susceptibility prediction. The model is trained on a comprehensive dataset comprising 19,898 samples, constructed from landslide records and 16 influencing factors in Kumamoto Prefecture, Japan. The input dataset is processed in tabular format using Microsoft Excel and includes variables such as topography, meteorology, soil characteristics, and human activity. The proposed model leverages Convolutional Neural Networks (CNN) to extract spatial features, Long Short-Term Memory networks (LSTM) to model temporal dependencies, and a Spatial Attention Mechanism (SAM) to enhance feature weighting dynamically. Experimental results demonstrate that the CNN–LSTM–SAM–Attention model significantly outperforms traditional machine learning approaches in terms of accuracy, precision, recall, F1 score, ROC–AUC, and PR–AUC. This substantial improvement is attributed to the model’s enhanced capability in capturing complex spatio-temporal patterns and dynamically weighting critical spatial features through the integrated Spatial Attention Mechanism (SAM). This study highlights the potential of deep learning-based approaches for improving the reliability of spatial landslide susceptibility prediction in complex terrain and dynamic climatic conditions. Full article

Lung cancer is a leading cause of cancer-related deaths globally, with current treatments having significant limitations, including drug resistance, metastasis, and tumor heterogeneity. This study investigated the anticancer potential of isalpinin, a flavonoid isolated from Paphiopedilum dianthum, against non-small cell lung cancer (NSCLC) cell lines A549, H23, and H460. Isalpinin significantly inhibited NSCLC cell viability in a dose- and time-dependent manner; H23 and H460 cells showed greater sensitivity (IC₅₀ a ~ 44 μM at 48 h) compared to A549 cells (IC₅₀ 82 μM). Isalpinin suppressed proliferation, migration, and anchorage-independent growth, particularly in H23/H460 cells. Mechanistically, it induced apoptosis via increased ROS production and Bcl-2 downregulation, particularly in H23 and H460 cells. In a molecular docking analysis, isalpinin was found to directly bind to the ATP-binding pocket of AKT1, as confirmed by reduced Akt/GSK3β phosphorylation. These results suggest that isalpinin showed a potent multi-target natural compound against NSCLC that disrupts the key hallmarks of malignancy and pro-survival signaling. However, its subtype-specific efficacy warrants further in vivo studies and an investigation of combinatorial therapeutic approaches to elucidate its clinical potential. Full article

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance. Full article

Traditional fiber-reinforced polymer (FRP) retrofit methods can restore the strength of reinforced concrete columns well, but stiffness is also partly restored. To increase the initial stiffness of retrofitted columns, this study investigated the seismic behavior of retrofitted resilient reinforced concrete (RRC) columns that were retrofitted by different methods, including high-strength mortar retrofit, carbon fiber-reinforced polymer (CFRP) retrofit, and CFRP and steel plate retrofit. In addition, the effect of the axial load was also considered. Quasi-static tests were conducted twice on five specimens, i.e., before and after repairing. The first test was used to create earthquake damage, and the second test was used to compare the seismic behavior of the retrofitted columns. The experimental results indicated that the CFRP retrofit method, whether with a steel plate or not, can restore the lateral resistance capacity well; furthermore, the drift-hardening behavior and self-centering performance were well maintained. The residual drift ratio of the CFRP-retrofitted column was less than 0.5%, even at a drift ratio of 3.5%, and less than 1% at the 6% drift ratio. However, the initial stiffness was only partly restored using the CFRP sheet. The introduction of steel plates was beneficial in restoring the initial stiffness, and the stiffness recovery rate remained above 90% when CFRP sheets and steel plates were used simultaneously. The strain distribution of the CFRP sheet showed that the steel plate did work at the initial loading stage, but the effect was limited. By using the steel plate, the CFRP hoop strain on the south side was reduced by 68% at the 6% drift ratio in the push direction and 38% in the pull direction. The axial strain of CFRP cannot be ignored due to the larger value than the hoop strain, which means that the biaxial stress condition should be considered when using an FRP sheet to retrofit RC columns. Full article