Continuously Tunable MOFs Enable Precise Mass Transfer for High-Performance Isomer Separation.

Modulating mass transfer is crucial for optimizing the catalytic and separation performances of porous materials. Here, we systematically developed a series of continuously tunable MOFs (CTMOFs) that exhibit incessantly increased mass transfer. This was achieved through the strategic blending of ligands with different lengths and ratios in MOFs featuring the fcu topology. By employing a proportional mixture of two ligands in the synthesis of UiO-66, the micropores expanded, facilitating faster mass transfer. The mass transfer rate was evaluated by dye adsorption, dark-field microscopy, and gas chromatography (GC). The GC performance proved that both too-fast and too-slow mass transfer led to low separation performance. The optimized mass transfer in CTMOFs resulted in an exceptionally high separation resolution (5.96) in separating p-xylene and o-xylene. Moreover, this study represents the first successful use of MOFs for high-performance separation of propylene and propane by GC. This strategy provides new inspiration in regulating mass transfer in porous materials.

Identification of the novel biomarkers involved in the mitochondrial metabolism-related reactive oxygen species and their role in lung cancer T-cell exhaustion and immunotherapy.

Purpose: To study the role of mitochondrial metabolism and obtain novel biomarkers in immunotherapy for non-small cell lung cancer (NSCLC). Methods: We collected the 188 genes involved in mitochondrial metabolism(MMGs) from the MSIGDB project and then quantified the activity of mitochondrial metabolism. All the NSCLC patients were divided into C1 and C2 clusters based on the 26 prognosis-related MMGs. The differences in biology, differential immune microenvironment, chronic hypoxia and prognosis between C1 and C2 patients were also analyzed. In addition, we validated the results of bioinformatics analysis in lung cancer tissues and cell lines. Results: Patients in the C2 cluster had a higher level of mitochondrial metabolism. Patients in the C2 cluster responded better to immunotherapy and had a lower level of T-cell exclusion. The markers of T-cell failure were upregulated in the C1 patients. Hypoxia can lead to a high percentage of C1 patients. ADH1C might be involved in mitochondrial metabolism and immunotherapy response, which can be affected by hypoxia, making it an underlying biomarker. The expression levels of ADH1C in BEAS-2B, H1299, A549 and H460 cells were detected, revealing that ADH1C is upregulated in lung cancer cells. We observed that patients with low ADH1C expression had a longer survival time. The enzyme activities of HK, PK, LDH and SDH were significantly reduced in H1299 and H460 cells with ADH1C knockdown, along with more ROS. Furthermore, the expression levels of PD-L1 and HHLA2 in tumor tissues were analyzed, which found that ADH1C was significantly positively correlated with the expression of PD-L1 and HHLA2. Conclusions: In summary, our study comprehensively explored the molecules involved in mitochondrial metabolism and their role in immunotherapy and T lymphocyte failure.

Facile synthesis of manganese-hafnium nanocomposites for multimodal MRI/CT imaging and in vitro photodynamic therapy of colon cancer.

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn3O4-HfO2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn3O4 NPs and Mn3O4-HfO2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn3O4-HfO2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn3O4-HfO2 NCs exhibit significant enhancement in T1-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn3O4-HfO2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn3O4-HfO2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm-2) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn3O4-HfO2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy.

Climate change market-driven poleward shifts in cropland production create opportunities for tropical biodiversity conservation and habitat restoration.

Although the impacts of climate change on the yields of crops have been studied, how these changes will result in the eventual realized crop production through market feedbacks has received little attention. Using a combination of attainable yield predictions for wheat, rice, maize, soybean and sugarcane, computable general equilibrium and land rent models, we project market impacts and crop-specific land-use change up to 2100 and the resulting implications for carbon and biodiversity. The results show a general increase in crop prices in tropical regions and a decrease in sub-tropical and temperate regions. Land-use change driven by market feedbacks generally amplify the effects of climate change on yields. Wheat, maize and sugarcane are projected to experience the most expansion especially in Canada and Russia, which also present the highest potential for habitat conversion-driven carbon emissions. Conversely, Latin America presents the highest extinction potential for birds, mammals and amphibians due to cropland expansion. Climate change is likely to redistribute agricultural production, generating market-driven land-use feedback effects which could, counterintuitively, protect global biodiversity by shifting global food production towards less-biodiverse temperate regions while creating substantial restoration opportunities in the tropics.

Sorafenib-Encapsulated Liposomes to Activate Hypoxia-Sensitive Tirapazamine for Synergistic Chemotherapy of Hepatocellular Carcinoma.

Combination therapy with the synergistic effect is an effective way in cancer chemotherapy. Herein, an antiangiogenic sorafenib (SOR) and hypoxia-activated prodrug tirapazamine (TPZ)-coencapsulated liposome (LipTPZ/SOR) is prepared for chemotherapy of hepatocellular carcinoma (HCC). SOR is a multi-target tyrosine kinase inhibitor that can inhibit tumor cell proliferation and angiogenesis. The antiangiogenesis effect of SOR can reduce oxygen supply and aggravate tumor hypoxia, which is able to activate hypoxia-sensitive prodrug TPZ, exhibiting the synergistic antitumor effect. LipTPZ/SOR at different molar ratios of TPZ and SOR can significantly inhibit the proliferation of hepatocellular carcinoma cells. The mole ratio of TPZ and SOR was optimized to 2:1, which exhibited the best synergetic antitumor effect. The synergistic antitumor mechanism of SOR and TPZ was also investigated in vivo. After treated with SOR, the number of vessels was decreased, and the degree of hypoxia was aggravated in tumor tissues. What is more, in the presence of SOR, TPZ could be activated to inhibit tumor growth. The combination of TPZ and SOR exhibited an excellent synergistic antitumor effect. This research not only provides an innovative strategy to aggravate tumor hypoxia to promote TPZ activation but also paints a blueprint about a new nanochemotherapy regimen for the synergistic chemotherapy of HCC, which has excellent biosafety and bright clinical application prospects.

A multicenter case-controlled study on laparoscopic hepatectomy versus microwave ablation as first-line therapy for 3-5 cm hepatocellular carcinoma in patients aged 60 and older.

BACKGROUND: There is currently a lack of convincing evidence for microwave ablation (MWA) and laparoscopic liver resection (LLR) for patients ≥60 years old with 3-5 cm hepatocellular carcinoma. MATERIALS AND METHODS: Patients were divided into three cohorts based on restricted cubic spline analysis: 60-64, 65-72, and ≥73 years. Propensity score matching (PSM) was performed to balance the baseline variables in a 1:1 ratio. Overall survival (OS) and disease-free survival (DFS) were assessed, followed by a comparison of complications, hospitalization, and cost. RESULTS: Among 672 patients, the median age was 66 (IQR 62-71) years. After PSM, two groups of 210 patients each were selected. During the 36.0 (20.4-52.4) month follow-up period, the 1-year, 3-year, and 5-year OS rates in the MWA group were 97.6, 80.9, and 65.3% and 95.5, 78.7, and 60.4% in the LLR group (HR 0.98, P =0.900). The corresponding DFS rates were 78.6, 49.6, and 37.5% and 82.8, 67.8, and 52.9% (HR 1.52, P =0.007). The 60-64 age cohort involved 176 patients, with no a significant difference in OS between the MWA and LLR groups (HR 1.25, P =0.370), MWA was associated with a higher recurrence rate (HR 1.94, P =0.004). A total of 146 patients were matched in the 65-72 age cohort, with no significant differences in OS and DFS between the two groups (OS (HR 1.04, P =0.900), DFS (HR 1.56, P =0.110)). In 76 patients aged ≥73 years after PSM, MWA provided better OS for patients (HR 0.27, P =0.015), and there were no significant differences in DFS between the two groups (HR 1.41, P =0.380). Taken together, for patients older than 65 years, the recurrence rate of MWA was comparable with LLR. Safety analysis indicated that LLR was associated with more postoperative bleeding ( P =0.032) and hypoproteinemia ( P =0.024). CONCLUSIONS: MWA was comparable to LLR in patients aged 65 years and older. MWA could be an alternative for the oldest old or the ill patients who cannot afford LLR, while LLR is still the first option of treatments for early-stage 3-5 cm hepatocellular carcinoma in capable elderly's.

Dumbbell-shaped bimetallic AuPd nanoenzymes for NIR-II cascade catalysis-photothermal synergistic therapy.

The noble metal NPs that are currently applied to photothermal therapy (PTT) have their photoexcitation location mainly in the NIR-I range, and the low tissue penetration limits their therapeutic effect. The complexity of the tumor microenvironment (TME) makes it difficult to inhibit tumor growth completely with a single therapy. Although TME has a high level of H2O2, the intratumor H2O2 content is still insufficient to catalyze the generation of sufficient hydroxide radicals (‧OH) to achieve satisfactory therapeutic effects. The AuPd-GOx-HA (APGH) was obtained from AuPd bimetallic nanodumbbells modified by glucose oxidase (GOx) and hyaluronic acid (HA) for photothermal enhancement of tumor starvation and cascade catalytic therapy in the NIR-II region. The CAT-like activity of AuPd alleviates tumor hypoxia by catalyzing the decomposition of H2O2 into O2. The GOx-mediated intratumoral glucose oxidation on the one hand can block the supply of energy and nutrients essential for tumor growth, leading to tumor starvation. On the other hand, the generated H2O2 can continuously supply local O2, which also exacerbates glucose depletion. The peroxidase-like activity of bimetallic AuPd can catalyze the production of toxic ‧OH radicals from H2O2, enabling cascade catalytic therapy. In addition, the high photothermal conversion efficiency (η = 50.7 %) of APGH nanosystems offers the possibility of photothermal imaging-guided photothermal therapy. The results of cell and animal experiments verified that APGH has good biosafety, tumor targeting, and anticancer effects, and is a precious metal nanotherapeutic system integrating glucose starvation therapy, nano enzyme cascade catalytic therapy, and PTT therapy. This study provides a strategy for photothermal-cascade catalytic synergistic therapy combining both exogenous and endogenous processes. STATEMENT OF SIGNIFICANCE: AuPd-GOx-HA cascade nanoenzymes were prepared as a potent cascade catalytic therapeutic agent, which enhanced glucose depletion, exacerbated tumor starvation and promoted cancer cell apoptosis by increasing ROS production through APGH-like POD activity. The designed system has promising photothermal conversion ability in the NIR-II region, simultaneously realizing photothermal-enhanced catalysis, PTT, and catalysis/PTT synergistic therapy both in vitro and in vivo. The present work provides an approach for designing and developing catalytic-photothermal therapies based on bimetallic nanoenzymatic cascades.

Precisión diagnóstica de la TC-RFF con un nuevo algoritmo de subpíxel grueso a fino en la detección de isquemia específica de lesión: un estudio multicéntrico prospectivo / Diagnostic accuracy of CT-FFR with a new coarse-to-fine subpixel algorithm in detecting lesion-specific ischemia: a prospective multicenter study

Introduction and objectives A new computed tomography-derived fractional flow reserve (CT-FFR) technique with a “coarse-to-fine subpixel” algorithm has been developed to generate precise lumen contours. The aim of this study was to assess the diagnostic performance of this new CT-FFR algorithm for discriminating lesion-specific ischemia using wire-based FFR ≤ 0.80 as the reference standard in patients with coronary artery disease. Methods This prospective, multicenter study screened 330 patients undergoing coronary CT angiography (CCTA) and invasive FFR (median interval 2 days) from 6 tertiary hospitals. CT-FFR was evaluated in a blinded fashion with a “coarse-to-fine subpixel” algorithm for lumen contour. Results Between March 2019 and May 2020, we included 316 patients with 324 vessels. There was a good correlation between CT-FFR and invasive FFR (r=0.76, P<.001). The diagnostic sensitivity, specificity, and accuracy on a per-vessel level were 95.3%, 89.8%, and 92.0% for CT-FFR, and 96.4%, 26.4%, and 53.1% for CCTA>50% stenosis, respectively. CT-FFR showed improved discrimination of ischemia compared with CCTA alone overall (AUC, 0.95 vs 0.74, P<.001) and in intermediate (AUC, 0.96 vs 0.62, P<.001) and “gray zone” lesions (AUC, 0.88 vs 0.61, P<.001). The diagnostic specificity, accuracy, and AUC for CT-FFR (71.9%, 82.8%, and 0.84) outperformed CCTA (9.4%, 48.3%, and 0.66) in patients or in vessels with severe calcification (all P<.05). Conclusions CT-FFR with a new “coarse-to-fine subpixel” algorithm showed high performance in identifying hemodynamically significant stenosis. The diagnostic performance of CT-FFR was superior to that of CCTA in intermediate lesions, “gray zone” lesions, and severely calcified lesions (AU)

Introducción y objetivos Se ha desarrollado una nueva técnica basada en tomografía computarizada para la evaluación de la reserva fraccional de flujo (TC-RFF) con un algoritmo de subpíxel «de grueso a fino» para generar contornos luminales precisos. El objetivo de este estudio es evaluar el rendimiento diagnóstico de este nuevo algoritmo de TC-RFF para discriminar la isquemia específica de lesión utilizando la evaluación invasiva de la RFF ≤ 0,80 como referencia en pacientes con enfermedad coronaria. Métodos Este estudio prospectivo y multicéntrico evaluó a 330 pacientes sometidos a angiografía coronaria no invasiva con TC (ACTC) y evaluación invasiva de la RFF (mediana del intervalo, 2 días) en 6 hospitales terciarios. La TC-RFF se evaluó a ciegas con un algoritmo de subpíxel «de grueso a fino» para la evaluación de la luz. Resultado Entre marzo de 2019 y mayo de 2020, se incluyó a un total de 316 pacientes con 324 vasos. Hubo una buena correlación entre la TC-RFF y la evaluación invasiva de la RFF (r=0,76; p<0,001). La sensibilidad, la especificidad y la exactitud diagnóstica por vaso fueron, respectivamente, del 95,3, el 89,8 y el 92,0% para la TC-RFF y del 96,4, el 26,4 y el 53,1% para la ACTC para las estenosis>50%. La TC-RFF mostró mejor discriminación de la isquemia que la ACTC sola en general (ABC=0,95 frente a ABC=0,74; p<0,001) y en lesiones intermedias (ABC=0,96 frente a ABC=0,62; p<0,001) y en «zona gris» (ABC=0,88 frente a ABC=0,61; p<0,001). La especificidad, la exactitud y el ABC diagnóstica de la TC-RFF (el 71,9%, el 82,8% y 0,84) superaron las de la ACTC (el 9,4%, el 48,3% y 0,66) en pacientes o vasos con calcificación grave (todos, p<0,05). Conclusiones La TC-RFF con un algoritmo de subpíxel «de grueso a fino» proporcionó un alto rendimiento en la identificación de estenosis hemodinámicamente significativas. El rendimiento diagnóstico de la TC-RFF fue superior al de la ACTC en lesiones intermedias, de «zona gris» y con calcificación grave (AU)

Multi-Dimensional Wi-Fi Received Signal Strength Indicator Data Augmentation Based on Multi-Output Gaussian Process for Large-Scale Indoor Localization.

Location fingerprinting using Received Signal Strength Indicators (RSSIs) has become a popular technique for indoor localization due to its use of existing Wi-Fi infrastructure and Wi-Fi-enabled devices. Artificial intelligence/machine learning techniques such as Deep Neural Networks (DNNs) have been adopted to make location fingerprinting more accurate and reliable for large-scale indoor localization applications. However, the success of DNNs for indoor localization depends on the availability of a large amount of pre-processed and labeled data for training, the collection of which could be time-consuming in large-scale indoor environments and even challenging during a pandemic situation like COVID-19. To address these issues in data collection, we investigate multi-dimensional RSSI data augmentation based on the Multi-Output Gaussian Process (MOGP), which, unlike the Single-Output Gaussian Process (SOGP), can exploit the correlation among the RSSIs from multiple access points in a single floor, neighboring floors, or a single building by collectively processing them. The feasibility of MOGP-based multi-dimensional RSSI data augmentation is demonstrated through experiments using the hierarchical indoor localization model based on a Recurrent Neural Network (RNN)-i.e., one of the state-of-the-art multi-building and multi-floor localization models-and the publicly available UJIIndoorLoc multi-building and multi-floor indoor localization database. The RNN model trained with the UJIIndoorLoc database augmented with the augmentation mode of "by a single building", where an MOGP model is fitted based on the entire RSSI data of a building, outperforms the other two augmentation modes and results in the three-dimensional localization error of 8.42 m.

Safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer.

PURPOSE: To evaluate the safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer. MATERIALS AND METHODS: A total of 27 patients with 40 liver lesions underwent fluorescence-assisted laparoscopic ablation between January 2020 to March 2023. The sensitivity of indocyanine green (ICG)-fluorescence imaging, technique effectiveness rate and complications of fluorescence-assisted laparoscopic thermal ablation were evaluated. RESULTS: In total, 33 out of the 40 lesions were identified by ICG-fluorescence imaging technique, with the sensitivity of 82.5%. The sensitivity of ICG-fluorescence imaging of tumor detection in liver surface of parenchyma was significantly higher than that in the deeply located hepatic parenchyma (96.8% vs 33.3%, p = 0.002). ICG-fluorescence imaging procedures detected 4 lesions that cannot be seen on intraoperative ultrasound. It provides clear demarcation lines on the hepatic surface. Technical success is achieved if the necrotic zone had at least a 5 mm ablative margin around the outer edge of the ICG-fluorescence image. Technical success of fluorescence laparoscopic radiofrequency ablation (FLRFA) and fluorescence laparoscopic microwave ablation (FLMWA) was 100% (27/27). Technical effectiveness is defined by the complete necrotic lesions of the local tumor tissue during follow-up. According to the CT/MRI one month after FLRFA or FLMWA, the technical efficacy rate was 92.5% (37/40) and local tumor progression occurred in 7.5% (3/40) of the enrolled lesions. During the follow-up period, no major complications were observed. CONCLUSION: ICG-fluorescence imaging guided laparoscopic thermal ablation was feasible, safe and effective.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

The Emerging Landscape for Combating Resistance Associated with Energy-Based Therapies via Nanomedicine.

Cancer represents a serious disease with significant implications for public health, imposing substantial economic burden and negative societal consequences. Compared to conventional cancer treatments, such as surgery and chemotherapy, energy-based therapies (ET) based on athermal and thermal ablation provide distinct advantages, including minimally invasive procedures and rapid postoperative recovery. Nevertheless, due to the complex pathophysiology of many solid tumors, the therapeutic effectiveness of ET is often limited. Nanotechnology offers unique opportunities by enabling facile material designs, tunable physicochemical properties, and excellent biocompatibility, thereby further augmenting the outcomes of ET. Numerous nanomaterials have demonstrated the ability to overcome intrinsic therapeutic resistance associated with ET, leading to improved antitumor responses. This comprehensive review systematically summarizes the underlying mechanisms of ET-associated resistance (ETR) and highlights representative applications of nanoplatforms used to mitigate ETR. Overall, this review emphasizes the recent advances in the field and presents a detailed account of novel nanomaterial designs in combating ETR, along with efforts aimed at facilitating their clinical translation.

Identification and Analysis of DNA Methylation Inflammation-Related Key Genes in Intracerebral Hemorrhage.

Inflammation and DNA methylation have been reported to play key roles in intracerebral hemorrhage (ICH). This study aimed to investigate new diagnostic biomarkers associated with inflammation and DNA methylation using a comprehensive bioinformatics approaches. GSE179759 and GSE125512 were collected from the Gene Expression Omnibus database, and 3222 inflammation-related genes (IFRGs) were downloaded from the Molecular Signatures Database. Key differentially expressed methylation-regulated and inflammation-related genes (DE-MIRGs) were identified by overlapping methylation-regulated differentially expressed genes (MeDEGs) between patients with ICH and control samples, module genes from weighted correlation network analysis, and IFRGs. Functional annotation of DE-MIRGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) network was constructed to clarify the interrelationships between different DE-MIRGs. The key genes were categorized by least absolute shrinkage selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE), and gene set enrichment analysis (GSEA). A total of 22 DE-MIRGs were acquired from 451 MeDEGs, 3222 IFRGs, and 302 module genes, and were mainly enriched in the GO terms of wound healing, blood coagulation, and hemostasis; and the KEGG pathways of PI3K/Akt signaling, focal adhesion, and regulation of actin cytoskeleton. A PPI network with 22 nodes and 87 edges was constructed based on the 22 DE-MIRGs, 11 of which were selected for key gene selection. Two 2 key genes (SELP and S100A4) were identified using LASSO and SVM-RFE. Finally, SELP was mainly enriched in cell morphogenesis involved in differentiation, cytoplasmic translation, and actin binding of GO terms, and the KEGG pathway including endocytosis, focal adhesion, and platelet activation. S100A4 was mainly enriched in GO terms including mitochondrial inner membrane; mitochondrial respirasome and lysosomal membrane; and the KEGG pathway of oxidative phosphorylation, regulation of actin cytoskeleton, and chemical carcinogenesis-reactive oxygen species. Twenty-two DE-MIRGs-associated inflammation and DNA methylation were identified between patients with ICH and normal controls, and two key genes (SELP and S100A4) were identified and regarded as biomarkers for ICH, which could provide the research foundation for further investigation of the pathological mechanism of ICH.

Diagnostic accuracy of CT-FFR with a new coarse-to-fine subpixel algorithm in detecting lesion-specific ischemia: a prospective multicenter study.

INTRODUCTION AND OBJECTIVES: A new computed tomography-derived fractional flow reserve (CT-FFR) technique with a "coarse-to-fine subpixel" algorithm has been developed to generate precise lumen contours. The aim of this study was to assess the diagnostic performance of this new CT-FFR algorithm for discriminating lesion-specific ischemia using wire-based FFR ≤ 0.80 as the reference standard in patients with coronary artery disease. METHODS: This prospective, multicenter study screened 330 patients undergoing coronary CT angiography (CCTA) and invasive FFR (median interval 2 days) from 6 tertiary hospitals. CT-FFR was evaluated in a blinded fashion with a "coarse-to-fine subpixel" algorithm for lumen contour. RESULTS: Between March 2019 and May 2020, we included 316 patients with 324 vessels. There was a good correlation between CT-FFR and invasive FFR (r=0.76, P<.001). The diagnostic sensitivity, specificity, and accuracy on a per-vessel level were 95.3%, 89.8%, and 92.0% for CT-FFR, and 96.4%, 26.4%, and 53.1% for CCTA>50% stenosis, respectively. CT-FFR showed improved discrimination of ischemia compared with CCTA alone overall (AUC, 0.95 vs 0.74, P<.001) and in intermediate (AUC, 0.96 vs 0.62, P<.001) and "gray zone" lesions (AUC, 0.88 vs 0.61, P<.001). The diagnostic specificity, accuracy, and AUC for CT-FFR (71.9%, 82.8%, and 0.84) outperformed CCTA (9.4%, 48.3%, and 0.66) in patients or in vessels with severe calcification (all P<.05). CONCLUSIONS: CT-FFR with a new "coarse-to-fine subpixel" algorithm showed high performance in identifying hemodynamically significant stenosis. The diagnostic performance of CT-FFR was superior to that of CCTA in intermediate lesions, "gray zone" lesions, and severely calcified lesions. Clinical Trial Register: NCT04731285.

Lonidamine liposomes to enhance photodynamic and photothermal therapy of hepatocellular carcinoma by inhibiting glycolysis.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.

Synthesis of Multifunctional Mn3O4-Ag2S Janus Nanoparticles for Enhanced T1-Magnetic Resonance Imaging and Photo-Induced Tumor Therapy.

The global burden of cancer is increasing rapidly, and nanomedicine offers promising prospects for enhancing the life expectancy of cancer patients. Janus nanoparticles (JNPs) have garnered considerable attention due to their asymmetric geometry, enabling multifunctionality in drug delivery and theranostics. However, achieving precise control over the self-assembly of JNPs in solution at the nanoscale level poses significant challenges. Herein, a low-temperature reversed-phase microemulsion system was used to obtain homogenous Mn3O4-Ag2S JNPs, which showed significant potential in cancer theranostics. Structural characterization revealed that the Ag2S (5-10 nm) part was uniformly deposited on a specific surface of Mn3O4 to form a Mn3O4-Ag2S Janus morphology. Compared to the single-component Mn3O4 and Ag2S particles, the fabricated Mn3O4-Ag2S JNPs exhibited satisfactory biocompatibility and therapeutic performance. Novel diagnostic and therapeutic nanoplatforms can be guided using the magnetic component in JNPs, which is revealed as an excellent T1 contrast enhancement agent in magnetic resonance imaging (MRI) with multiple functions, such as photo-induced regulation of the tumor microenvironment via producing reactive oxygen species and second near-infrared region (NIR-II) photothermal excitation for in vitro tumor-killing effects. The prime antibacterial and promising theranostics results demonstrate the extensive potential of the designed photo-responsive Mn3O4-Ag2S JNPs for biomedical applications.

Excitation Wavelength-Dependent Fluorescence of a Lanthanide Organic Metal Halide Cluster for Anti-Counterfeiting Applications.

The achievement of significant photoluminescence (PL) in lanthanide ions (Ln3+ ) has primarily relied on host sensitization, where energy is transferred from the excited host material to the Ln3+ ions. However, this luminous mechanism involves only one optical antenna, namely the host material, which limits the accessibility of excitation wavelength-dependent (Ex-De) PL. Consequently, the wider application of Ln3+ ions in light-emitting devices is hindered. In this study, we present an organic-inorganic compound, (DMA)4 LnCl7 (DMA+ =[CH3 NH2 CH3 ]+ , Ln3+ =Ce3+ , Tb3+ ), which serves as an independent host lattice material for efficient Ex-De emission by doping it with trivalent antimony (Sb3+ ). The pristine (DMA)4 LnCl7 compounds exhibit high luminescence, maintaining the characteristic sharp emission bands of Ln3+ and demonstrating a high PL quantum yield of 90-100 %. Upon Sb3+ doping, the compound exhibits noticeable Ex-De emission with switchable colors. Through a detailed spectral study, we observe that the prominent energy transfer process observed in traditional host-sensitized systems is absent in these materials. Instead, they exhibit two independent emission centers from Ln3+ and Sb3+ , each displaying distinct features in luminous color and radiative lifetime. These findings open up new possibilities for designing Ex-De emitters based on Ln3+ ions.

Fractional flow reserve versus intravascular imaging to guide decision-making for percutaneous coronary intervention in intermediate lesions: A meta-analysis.

BACKGROUND: Both fractional flow reserve (FFR) and intravascular imaging (IVI) have been used to guide the decision-making for percutaneous coronary intervention (PCI) in intermediate coronary stenosis. Nevertheless, studies that directly compared the prognostic significance of these two strategies are scarce. AIMS: The aim of this meta-analyses was to evaluate the impact of FFR versus IVI to guide the decision-making in PCI for intermediate stenosis on clinical outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane, and relevant database from inception date to September 2022 for observational studies and randomized clinical trials (RCTs) which compared FFR and IVI-based decision-making in PCI for intermediate stenosis. The primary outcome was a composite of major adverse cardiac event (MACE). Pooled risk ratios (RR) were calculated using random effects models and heterogeneity were evaluated with the I2 statistic. RESULTS: We identified 5 studies (3 RCTs and 2 observational studies) with 3208 patients. The follow-up duration ranged from 12 to 24 months. Among five studies, four compared FFR with intravascular ultrasound while one compared FFR with optical coherence tomography. There was no statistically difference between FFR and IVI in the incidence of MACE (RR: 1.19; 95% confidence interval: 0.85-1.68; p = 0.31) and its individual components. These results were consistent regardless of various cut-off value of PCI across the studies. Compared with IVI, FFR was associated with a lower PCI rate (37.0% vs. 60.3%; p < 0.001). CONCLUSIONS: The decision to perform PCI for intermediate stenosis guided by FFR or IVI showed a similar clinical outcome. The use of FFR significantly reduced the need for PCI.

Xanthohumol attenuates renal ischemia/reperfusion injury by inhibiting ferroptosis.

Ischemia/reperfusion injury (IRI) is a notable contributor to kidney injury, but effective prevention and treatment options are limited. The present study aimed to evaluate the impact of xanthohumol (XN), a kind of flavonoid, on renal IRI and its pathological process in rats. Rats and HK-2 cells were divided into five groups: Sham (control), IR [hypoxia-reoxygenation (HR)], IR (HR) + XN, IR (HR) + erastin or IR (HR) + XN + erastin. The effects of XN and erastin (a ferroptosis inducer) on IRI in rats were evaluated using blood urea nitrogen, plasma creatinine, glutathione, superoxide dismutase and malondialdehyde kits, western blotting, cell viability assay, hematoxylin and eosin staining and reactive oxygen species (ROS) detection. Nrf2 small interfering (si)RNA was used to investigate the role of the Nrf2/heme oxygenase (HO)-1 axis in XN-mediated protection against HR injury. Cell viability, ROS levels and expression of ferroptosis-related proteins were analyzed. Following IR, renal function of rats was severely impaired and oxidative stress and ferroptosis levels significantly increased. However, XN treatment decreased renal injury and inhibited oxidative stress and ferroptosis in renal tubular epithelial cells. Additionally, XN upregulated the Nrf2/HO-1 signaling pathway and Nrf2-siRNA reversed the renoprotective effect of XN. XN effectively decreased renal IRI by inhibiting ferroptosis and oxidative stress and its protective mechanism may be associated with the Nrf2/HO-1 signaling pathway.

Salidroside inhibits renal ischemia/reperfusion injury­induced ferroptosis by the PI3K/AKT signaling pathway.

Renal ischemia/reperfusion injury (RIRI) represents the principal factor underlying acute kidney injury (AKI), which primarily stems from cellular injuries and ferroptosis caused by reactive oxygen species (ROS). Salidroside (SA), an antioxidant natural ester, has been attributed with the potential to protect against RIRI. In the present study, rats received daily SA doses (1, 10, or 100 mg/kg) by gavage for 7 consecutive days before surgery. The results revealed aggravated renal injury in the RIRI group, which was effectively prevented by SA pretreatment (10 and 100 mg/kg), with the 1 mg/kg dosage demonstrating lesser efficacy. Additionally, the results indicated that SA pretreatment mitigated the RIRI-related upregulation of antioxidative superoxide dismutase. In vitro studies corroborated SA's ability to maintain hypoxia/reoxygenation-treated NRK cell viability, with the protective effect being observed at SA concentrations ≥1 µM and peaking at 100 µM. Furthermore, the results showed that SA safeguarded renal tubular epithelial cells from oxidative damage, reduced ROS accumulation, and inhibited ferroptosis via activation of the PI3K/AKT signaling pathway. Therefore, the results of the present study highlight the promising therapeutic potential of SA as an effective intervention for RIRI via targeting of PI3K/AKT signaling pathway-mediated anti-oxidative and anti-ferroptotic mechanisms.