Lipid metabolism in tumor-infiltrating regulatory T cells: perspective to precision immunotherapy.

Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive inflammation and mediate tumor development. The abundance of Tregs in tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However, immunotherapy targeting Tregs has been severely hampered by autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target tumor-infiltrating immune cells, and lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which lipid accumulation confers a metabolic advantage to tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint therapy.

Adavosertib-encapsulated metal-organic frameworks for p53-mutated gallbladder cancer treatment via synthetic lethality.

Adavosertib (ADA) is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer (GBC). However, drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications. Herein, estrone-targeted ADA-encapsulated metal-organic frameworks (ADA@MOF-EPL) for GBC synthetic lethal treatment by inducing conditional factors are developed. The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment. Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species (ROS), which leads to a further increase in DNA damage, resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality. The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity. Moreover, ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors, revealing its potential as a broad-spectrum antitumor drug.

Understanding the audience in framing research: empirical evidence from three studies examining HIV framing in China.

Guided by framing theory, this three-phase mixed-methods study explored (a) how Chinese government-sponsored newspapers frame HIV and (b) framing effects on people's HIV beliefs. A content analysis of two government-sponsored newspapers and a survey of 210 readers showed discrepancies in frame and frame valence. In-depth follow-up interviews with 15 media and public health experts revealed that the discrepancies were related to people's attitudes toward the media and beliefs about HIV, which could further be explained by the political environment, media ecology, historical framing, and cultural identities in China. We discuss theoretical implications for framing theory and practical implications for HIV media coverage.

Pre-activated nanoparticles with persistent luminescence for deep tumor photodynamic therapy in gallbladder cancer.

Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

Estimating the influencing factors for T1b/T2 gallbladder cancer on survival and surgical approaches selection.

BACKGROUND: The influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC. METHODS: We retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease-free survival (DFS), surgery-related outcomes, and surgical approaches were collected. RESULTS: A total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT (p < 0.001). There was no significance in OS (p = 0.790), DFS (p = 0.580), and surgery-related outcomes (all p > 0.05) between both groups. Decreased referrals (p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation (p = 0.004) were all associated with better OS, while fewer positive LNs (p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery-related outcomes between different TTT groups of incidental GBC patients (all p > 0.05). CONCLUSIONS: Positive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery-related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.

In Situ Synthesis of Ni-BTC Metal-Organic Framework@Graphene Oxide Composites for High-Performance Supercapacitor Electrodes.

In response to serious ecological and environmental problems worldwide, a novel graphene oxide (GO) induction method for the in situ synthesis of GO/metal organic framework (MOF) composites (Ni-BTC@GO) for supercapacitors with excellent performance is presented in this study. For the synthesis of the composites, 1,3,5-benzenetricarboxylic acid (BTC) is used as an organic ligand due to its economic advantages. The optimum amount of GO is determined by a comprehensive analysis of morphological characteristics and electrochemical tests. 3D Ni-BTC@GO composites show a similar spatial structure to that of Ni-BTC, revealing that Ni-BTC could provide an effective framework and avoid GO aggregation. The Ni-BTC@GO composites have a more stable electrolyte-electrode interface and an improved electron transfer route than pristine GO and Ni-BTC. The synergistic effects of GO dispersion and Ni-BTC framework on electrochemical behavior are determined, where Ni-BTC@GO 2 achieves the best performance in energy storage performance. Based on the results, the maximum specific capacitance is 1199 F/g at 1 A/g. Ni-BTC@GO 2 has an excellent cycling stability of 84.47% after 5000 cycles at 10 A/g. Moreover, the assembled asymmetric capacitor exhibits an energy density of 40.89 Wh/kg at 800 W/kg, and it still remains at 24.44 Wh/kg at 7998 W/kg. This material is expected to contribute to the design of excellent GO-based supercapacitor electrodes.

Hyperspectral remote sensing for tobacco quality estimation, yield prediction, and stress detection: A review of applications and methods.

Tobacco is an important economic crop and the main raw material of cigarette products. Nowadays, with the increasing consumer demand for high-quality cigarettes, the requirements for their main raw materials are also varying. In general, tobacco quality is primarily determined by the exterior quality, inherent quality, chemical compositions, and physical properties. All these aspects are formed during the growing season and are vulnerable to many environmental factors, such as climate, geography, irrigation, fertilization, diseases and pests, etc. Therefore, there is a great demand for tobacco growth monitoring and near real-time quality evaluation. Herein, hyperspectral remote sensing (HRS) is increasingly being considered as a cost-effective alternative to traditional destructive field sampling methods and laboratory trials to determine various agronomic parameters of tobacco with the assistance of diverse hyperspectral vegetation indices and machine learning algorithms. In light of this, we conduct a comprehensive review of the HRS applications in tobacco production management. In this review, we briefly sketch the principles of HRS and commonly used data acquisition system platforms. We detail the specific applications and methodologies for tobacco quality estimation, yield prediction, and stress detection. Finally, we discuss the major challenges and future opportunities for potential application prospects. We hope that this review could provide interested researchers, practitioners, or readers with a basic understanding of current HRS applications in tobacco production management, and give some guidelines for practical works.

Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis.

Aim: To determine if PD-L1 can be used as a biomarker to predict the efficacy of anti-PD-1/PD-L1 inhibitors in hepatocellular carcinoma (HCC). Methods: Relevant studies from a specific search of the four databases from October 2014 to December 2022 were included in this meta-analysis. Results: Higher PD-L1 expression levels were associated with a higher objective response rate (ORR). Higher PD-L1 expression levels on tumor cells and tumor proportion score were associated with higher ORR. PD-L1 was capable of predicting the effectiveness of nivolumab. Dako 28-8 is a promising assay for HCC. Conclusion: PD-L1 is a predictive biomarker for ORR in HCC. Tumor proportion score and PD-L1 expression levels on tumor cells are potential scoring algorithms.

Clinically, liver cancer patients with high PD-L1 levels may not benefit from immunotherapy. Conversely, some patients with low PD-L1 level can benefit from it. Therefore, the concept of PD-L1 as a predictive indicator in liver cancer is defective. Whether PD-L1 can serve as an indicator in liver cancer patients receiving immunotherapy needs urgent confirmation. In this work, we evaluated the feasibility of PD-L1 as a prognostic biomarker for immunotherapy. The results suggested that high expression of PD-L1 by tumor cells rather than tumor tissue was correlated with better prognosis.

Organo-Vermiculites Modified by Aza-Containing Gemini Surfactants: Efficient Uptake of 2-Naphthol and Bromophenol Blue.

To explore the effect of spacer structure on the adsorption capability of organo-vermiculites (organo-Vts), a series of aza-containing gemini surfactants (5N, 7N and 8N) are applied to modify Na-vermiculite (Na-Vt). Large interlayer spacing, strong binding strength and high modifier availability are observed in organo-Vts, which endow them with superiority for the adsorption of 2-naphthol (2-NP) and bromophenol blue (BPB). The maximum adsorption capacities of 5N-Vt, 7N-Vt and 8N-Vt toward 2-NP/BPB are 142.08/364.49, 156.61/372.65 and 146.50/287.90 mg/g, respectively, with the adsorption processes well fit by the PSO model and Freundlich isotherm. The quicker adsorption equilibrium of 2-NP than BPB is due to the easier diffusion of smaller 2-NP molecules into the interlayer space of organo-Vts. Moreover, stable regeneration of 7N-Vt is verified, with feasibility in the binary-component system that is demonstrated. A combination of theoretical simulation and characterization is conducted to reveal the adsorption mechanism; the adsorption processes are mainly through partition processes, electrostatic interaction and functional interactions, in which the spacer structure affects the interlayer environment and adsorptive site distribution, whereas the adsorbate structure plays a role in the diffusion process and secondary intermolecular interactions. The results of this study demonstrate the versatile applicability of aza-based organo-Vts targeted at the removal of phenols and dyes as well as provide theoretical guidance for the structural optimization and mechanistic exploration of organo-Vt adsorbents.

Architecting Nanostructured Co-BTC@GO Composites for Supercapacitor Electrode Application.

Herein, we present an innovative graphene oxide (GO)-induced strategy for synthesizing GO-based metal-organic-framework composites (Co-BTC@GO) for high-performance supercapacitors. 1,3,5-Benzene tricarboxylic acid (BTC) is used as an inexpensive organic ligand for the synthesis of composites. An optimal GO dosage was ascertained by the combined analysis of morphology characterization and electrochemical measurement. The 3D Co-BTC@GO composites display a microsphere morphology similar to that of Co-BTC, indicating the framework effect of Co-BTC on GO dispersion. The Co-BTC@GO composites own a stable interface between the electrolyte and electrodes, as well as a better charge transfer path than pristine GO and Co-BTC. A study was conducted to determine the synergistic effects and electrochemical behavior of GO content on Co-BTC. The highest energy storage performance was achieved for Co-BTC@GO 2 (GO dosage is 0.02 g). The maximum specific capacitance was 1144 F/g at 1 A/g, with an excellent rate capability. After 2000 cycles, Co-BTC@GO 2 maintains outstanding life stability of 88.1%. It is expected that this material will throw light on the development of supercapacitor electrodes that hold good electrochemical properties.

Functionalized UiO-66-NH2 by trimellitic acid for highly selective adsorption of basic blue 3 from aqueous solutions.

A novel metal-organic framework (MOF) UiO-66-TLA (UiO-66-Trimellitic Acid) was synthesized by one-pot method with trimellitic acid as modifier, which can effectively remove the basic dye Basic Blue 3 (BB3) in wastewater. Modification with carboxyl groups facilitates the adsorption of the cationic dye Basic Blue 3. The adsorption of BB3 by the modified UiO-66-TLA was significantly greater than that of its parent MOF. The adsorption capacity of the modified UiO-66-TLA for BB3 (234.23 mg g-1) was 93.2% higher than that of the original UiO-66-NH2 (121.24 mg g-1), this is closely related to the electrostatic interaction of -COOH in trimellitic acid. UiO-66-TLA was successfully synthesized as indicated by various characterization results. The adsorption kinetics conformed to the pseudo-second-order model, and the adsorption isotherm conformed to the Redlich-Peterson isotherm. This indicates that BB3 is a multi-parameter model of monolayer/multilayer arrangement on the adsorbent surface, and its rate-controlling step is chemisorption. The adsorption process was non-spontaneous and belonged to an endothermic reaction, in addition, it has great adsorption stability and regeneration The interaction of the modified UiO-66-TLA with BB3 was mainly affected by mechanisms, such as electrostatic interaction, π-π stacking as well as the abundant functional groups on UiO-66-TLA surface. These results demonstrate that UiO-66-TLA is an efficient, regenerable, water-stable material for the removal of BB3 in solution, with practical implications, suggesting its potential as a dye adsorbent.

Inhibition of AMPK/PFKFB3 mediated glycolysis synergizes with penfluridol to suppress gallbladder cancer growth.

BACKGROUND: Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have anticancer activity. However, the anticancer effects and underlying mechanisms of PF are not well-established in gallbladder cancer (GBC). METHODS: The anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration. RESULTS: In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the anticancer efficacy of PF on GBC. CONCLUSIONS: By inhibiting AMPK, the anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new light on the possibility of repurposing PF as an anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC. Video abstract.

Identification of invasion-metastasis associated MiRNAs in gallbladder cancer by bioinformatics and experimental validation.

BACKGROUND: Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation. METHODS: MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein-protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC. RESULTS: In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis. CONCLUSIONS: MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.

Do Messages Matter? Investigating the Combined Effects of Framing, Outcome Uncertainty, and Number Format on COVID-19 Vaccination Attitudes and Intention.

Guided by prospect theory, the current study aims to explore Chinese adults' attitudes and intention to get vaccinated against COVID-19 and investigate the effects of message frames (gain vs. loss), outcome uncertainty (certain vs. uncertain), and number format (frequency vs. percentage) on vaccination attitudes and intention. Participants (n = 413) were randomly assigned to one of the eight experimental conditions and participated in the online experiment. The results showed that Chinese adults' attitudes toward COVID-19 vaccination were highly favorable, and the vaccination intention was high; age and education were positively correlated with attitudes and intention. The results also showed that message frames, outcome uncertainty, and number format did not have significant main or interaction effects on vaccination attitudes and intention. The discussion focused on how Chinese culture and contextual factors may have influenced the results of the study, as well as the implications and suggestions for future studies.

Perceived facilitators and barriers to intentions of receiving the COVID-19 vaccines among elderly Chinese adults.

Elderly adults hold different beliefs regarding vaccination and are at higher risks for COVID-19 related illnesses and deaths. The current study aims to explore elderly (aged 65 or above) Chinese adults' intentions to get vaccinated against COVID-19 and the facilitators and barriers to vaccination intentions. We conducted in-depth interviews with 35 elderly adults in China through the lens of the integrative model of behavioral prediction. The results identified a number of facilitators, including convenience (both individual and collective), psychological and physiological wellbeing, collective wellbeing, supportive normative referents, and trust in the government, and some barriers, including vaccine ineffectiveness, side effects, safety, unsupportive normative referents, and the accessibility, affordability, and availability of COVID-19 vaccines. In addition, the results revealed participants' decision-making process: collective wellbeing and trust in the government overrode perceived barriers and perceived individual-level risks, which eventually overwhelmingly led to a high level of intentions to get vaccinated. Practical implications related to vaccine promotion and trust in the government were discussed.

They Are Just Light Bulbs, Right? The Personality Antecedents of Household Energy-Saving Behavioral Intentions among Young Millennials and Gen Z.

Small individual behaviors such as household energy-saving behaviors may have major environmental impacts. Individuals may combat global warming by replacing traditional light bulbs with more energy-efficient light bulbs such as LED bulbs, which save electricity and reduce greenhouse gas emissions. Guided by the integrative model of behavioral prediction, the current study explored the effects of five individual personality differences (i.e., consideration of future consequences, environmental value orientation, individualism and collectivism, regulatory focus, and self-monitoring) on young Millennials' and Gen Z's attitudes, perceived norms, perceived control, and intention to switch light bulbs. The results of a survey indicated that environmental value orientation, individualism and collectivism, regulatory focus, and self-monitoring all significantly predicted attitudes, perceived norms, and perceived control, which predicted behavioral intention. The findings suggested the complex psychological nuance of environmental protection behaviors, even among the "greenest" generations. Implications and directions for future studies were discussed.

[The new method monitoring crop water content based on NIR-Red spectrum feature space].

Moisture content is an important index of crop water stress condition, timely and effective monitoring of crop water content is of great significance for evaluating crop water deficit balance and guiding agriculture irrigation. The present paper was trying to build a new crop water index for winter wheat vegetation water content based on NIR-Red spectral space. Firstly, canopy spectrums of winter wheat with narrow-band were resampled according to relative spectral response function of HJ-CCD and ZY-3. Then, a new index (PWI) was set up to estimate vegetation water content of winter wheat by improveing PDI (perpendicular drought index) and PVI (perpendicular vegetation index) based on NIR-Red spectral feature space. The results showed that the relationship between PWI and VWC (vegetation water content) was stable based on simulation of wide-band multispectral data HJ-CCD and ZY-3 with R2 being 0.684 and 0.683, respectively. And then VWC was estimated by using PWI with the R2 and RMSE being 0.764 and 0.764, 3.837% and 3.840%, respectively. The results indicated that PWI has certain feasibility to estimate crop water content. At the same time, it provides a new method for monitoring crop water content using remote sensing data HJ-CCD and ZY-3.

[Estimating canopy water content in wheat based on new vegetation water index].

Moisture content is an important indicator for crop water stress condition, timely and effective monitoring crop water content is of great significance for evaluate crop water deficit balance and guide agriculture irrigation. In order to improve the saturated problems of different forms of typical NDWI (Normalized Different Water Index), we tried to introduce EVI (Enhanced Vegetation Index) to build new vegetation water indices (NDWI#) to estimate crop water content. Firstly, PROSAIL model was used to study the saturation sensitivity of NDWI, and NDWI# to canopy water content and LAI (Leaf Area Index). Then, the estimated model and verified model were estimated using the spectral data and moisture data in the field. The result showed that the new indices have significant relationships with canopy water content. In particular, by implementing modified standardized for NDWI1450, NDWI1940, NDWI2500. The result indicated that newly developed indices with visible-infrared and shortwave infrared spectral feature may have greater advantage for estimation winter canopy water content.