Low false-positive lymph nodes for 18F-fibroblast activation protein inhibitors PET/computed tomography in preoperative staging of patients with nonsmall cell lung cancer.

OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of 18F-fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in identifying primary tumors and mediastinal lymph node metastases in nonsmall cell lung cancer (NSCLC), with histopathological findings serving as the reference standard. METHODS: Nineteen patients underwent preoperative 18F-FAPI PET/CT and subsequent surgery; of these, 13 also underwent 18F-fluorodeoxyglucose (FDG) PET/CT within 1 week. The diagnostic accuracy of primary tumors and lymph node metastases was evaluated for both modalities. Semiquantitative parameters, including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBRs), for both primary tumors and lymph node metastases were assessed for both modalities. RESULTS: For primary tumors, 18 of 19 (94.7%) showed positive results on 18F-FAPI PET/CT scans. In 13 patients who also underwent 18F-FDG PET/CT, 18F-FAPI PET/CT demonstrated a higher detection rate compared with 18F-FDG PET/CT (100% vs. 69.1%). The overall accuracy of lymph node assessment with 18F-FAPI PET/CT (95.9-97.1%) was significantly higher compared to 18F-FDG PET/CT (51.0%). Malignant lymph nodes exhibited significantly higher SUVmax and TBR on 18F-FAPI scans (SUVmax: 7.0 vs. 0.9, P < 0.001; TBRmuscle: 5.0 vs. 0.8, P < 0.001) than on 18F-FDG scans (SUVmax: 3.9 vs. 1.8, P = 0.01), except for the liver TBR on 18F-FDG scans (TBRliver: 1.8 vs. 1.0, P = 0.055). CONCLUSION: 18F-FAPI could be utilized in the preoperative staging of NSCLC to mitigate the incidence of false positives associated with 18F-FDG, due to its higher accuracy in identifying mediastinal lymph node metastasis.

Therapeutic effects of natural compounds against diabetic complications via targeted modulation of ferroptosis.

Diabetes mellitus, a chronic metabolic disorder, can result in serious tissue and organ damage due to long-term metabolic dysfunction, leading to various complications. Therefore, exploring the pathogenesis of diabetic complications and developing effective prevention and treatment drugs is crucial. The role of ferroptosis in diabetic complications has emerged as a significant area of research in recent years. Ferroptosis, a recently discovered form of regulated cell death closely linked to iron metabolism imbalance and lipid peroxidation, has garnered increasing attention in studies exploring the potential role of natural products in its regulation. This review provides an overview of the mechanisms underlying ferroptosis, outlines detection methods, and synthesizes information from natural product databases. It also summarizes current research on how natural products may regulate ferroptosis in diabetic complications. Studies have shown that these products can modulate the ferroptosis process by influencing iron ion balance and combating oxidative stress. This highlights the potential of natural products in treating diabetic complications by regulating ferroptosis, offering a new strategy for managing such complications.

In Situ Closing the van der Waals Gap of Two-Dimensional Materials.

Self-intercalation in two-dimensional (2D) materials, converting 2D materials into ultrathin covalently bonded materials, presents great possibilities for studying a new family of quantum-confined materials with the potential to realize multifunctional behavior. However, understanding the mechanisms and associated in situ kinetics of synthesizing self-intercalated 2D (ic-2D) materials, particularly at the atomic scale, remains elusive, greatly hindering the practical applications of ic-2D crystals. Here, we successfully in situ synthesized ic-2D thin films via thermal annealing of their parental TMDCs inside an electron microscope. We atomically visualized the evolution from TaS2 and NbS2 into the corresponding ic-2D Ta1+xS2 and ic-2D Nb1+xS2, respectively, by in situ scanning transmission electron microscopy (STEM). The self-intercalation process in TaS2 is atomically realized by metal adatom edge adsorption and subsequent diffusion in an atom-by-atom manner. On the other hand, MoS2 and MoSe2 tend to coalesce into metal crystals under the same annealing conditions, suggesting that the self-intercalation process is predominantly controlled by thermodynamic factors as further verified by density functional theory (DFT). By varying the ramping rate and annealing temperature, the coverage and spatial arrangement of the filling sites can be precisely tuned, ranging from 2a × 3a, 3a × 3a, or Ta trimers, as predominantly gauged by kinetic factors. Our work sheds light on the thermodynamics and growth kinetics involved in ic-2D formation and paves the way for growing highly crystalline ic-2D materials with intercalation concentration and topology-dependent properties.

Assessing osteoporosis and bone mineral density through 18F-NaF uptake at lumbar spine.

OBJECTIVES: The use of 18F-Sodium fluoride (NaF) PET/CT is established in the detection of metastatic bone disease, yet its utility in osteoporosis remains underexplored. This research aims to assess the variations in 18F-NaF uptake among individuals with differing bone mineral density (BMD) and to examine the relationship between 18F-NaF uptake and BMD. METHODS: In this retrospective study, 199 patients (average age 56 ± 6, comprising 52 males and 147 females) with a history of cancer were analyzed. Each participant underwent both 18F-NaF PET/CT and lumbar dual-energy X-ray absorptiometry (DXA) scans within a span of 7 days. Based on DXA outcomes, patients and their lumbar vertebrae were categorized into normal BMD, osteopenia, and osteoporosis groups. The lumbar 18F-NaF uptake across these groups were compared, and to explore the association between lumbar standardized uptake values (SUV) values and BMD. The efficacy of 18F-NaF uptake in diagnosing osteoporosis or osteopenia was also evaluated. Analysis was conducted using Mann-Whitney U tests, Spearman regression, and receiver operating characteristic (ROC) curve analysis through GraphPad Prism 10.0. RESULTS: A total of 796 lumbar vertebrae from 199 patients were measured. It was observed that osteoporotic patients had significantly lower 18F-NaF uptake than those with osteopenia and normal BMD across the L1-L4 lumbar vertebrae (P < 0.0001). In a vertebra-based analysis, normal BMD vertebrae exhibited the highest maximum SUV(SUVmax) compared to osteopenic (8.13 ± 1.28 vs. 6.61 ± 1.01, P < 0.0001) and osteoporotic vertebrae (8.13 ± 1.28 vs. 4.82 ± 1.01, P < 0.0001). There was a positive correlation between lumbar 18F-NaF uptake and BMD across all vertebrae, with correlation coefficients exceeding 0.5 (range: 0.57-0.8). The area under the ROC curve values were notably high, at 0.96 for osteoporosis and 0.83 for osteopenia diagnosis. CONCLUSION: This study demonstrates distinct 18F-NaF uptake patterns among individuals with varying BMD levels, with a positive correlation between 18F-NaF uptake and BMD. These findings highlight the potential of 18F-NaF PET/CT as a supportive diagnostic method in the management of osteoporosis.

Phosphorus dynamics in volcanic soils of Weizhou Island, China: implications for environmental and agricultural applications.

The dynamics of phosphorus are intricately governed by geological and ecological processes. Examining phosphorus dynamics in volcanic islands can enhance our comprehension of its behavior within such unique geological systems. However, research on phosphorus dynamics in volcanic islands remains limited. We investigated the phosphorus content of volcaniclastic rocks and basalt soils from Weizhou Island, China, to understand the influencing factors on phosphorus dynamics. The results indicate that in the volcaniclastic profile, phosphorus concentrates at 20-40 cm (17 mg/kg), decreases at 40-60 cm (11.9 mg/kg), and increases at 80-200 cm up to 46.4 mg/kg proximate to the bedrock, for the basalt profile, phosphorus content increases from the surface (80.2 mg/kg) towards the bedrock (83.9 mg/kg). The differences in phosphorus distribution between volcaniclastic rocks and basalts reflect the influence of parent material, rock weathering degree, carbonate content, topographic elevation, sea level changes, and geological activities. A strong positive correlation (R = 0.96907) between total and available phosphorus has been observed, suggesting that total phosphorus content effectively predicts available phosphorus content. Volcaniclastic rocks in wharves and high-elevation areas show low total phosphorus, while forest land with dense vegetation and neutral to alkaline soil supports higher total phosphorus due to enhanced bioavailability for plant absorption and utilization. Overall, the basalt soil of the volcanic island Weizhou Island demonstrates superior long-term fertility compared to the volcaniclastic soil. Despite its low total phosphorus content, it mainly exists in a highly bioavailable form, facilitating plant absorption, which is crucial for enhancing agricultural yields and ecosystem restoration on volcanic islands.

Characteristics and phylogenetic analysis of the complete chloroplast genome of Mesembryanthemum cordifolium L. F. (Aizoaceae).

Mesembryanthemum cordifolium, a perennial plant with crassulacean acid metabolism (CAM) in the Aizoaceae family, has significant ornamental and medicinal values. In this study, we reported the first complete chloroplast genome sequence of this species. The total genome size was 153,734 bp in length, including a large single-copy (LSC) region of 85,692 bp, a small single-copy (SSC) region of 18,212 bp, and a pair of inverted repeat (IR) regions of 24,915 bp by each. The overall GC content of the M. cordifolium chloroplast genome was 37.08%. The genome encodes 131 genes, comprising 87 protein-coding genes (PCGs), 36 transfer RNA genes (tRNAs), and eight ribosomal RNA genes (rRNAs). Phylogenetic analysis shows this species was relatively close to M. crystallinum. This chloroplast genome sequence will be valuable for species discrimination and for understanding phylogenetic relationships within the genus Mesembryanthemum.

[Spatial Heterogeneity and Key Influencing Factors of Soil Organic Carbon, Soil Total Nitrogen, and Carbon to Nitrogen Ratio in main plantations of Torreya grandis cv. Merrillii].

Soil organic carbon （SOC） and soil total nitrogen （STN） serve as important indicators of the elemental balance within forest ecosystems reflecting soil fertility and quality. Accurate knowledge regarding the spatial variability of regional SOC, STN, and C∶N ratio and their influencing factors is of great significance for precise fertilization and soil health. In this study, a total of 117 topsoil samples （0-20 cm in depth） based on a 1 km×1 km grid were collected in the Torreya grandis cv. Merrillii plantation in Zhejiang Province. A combination of multi-dimensional statistical approaches （random forest model, structural equation model, redundancy analysis, and variation partitioning analysis） and diverse spatial analytical techniques （geostatistics, Moran's I index, etc.） were applied to reveal the spatial distributions and influencing factors of SOC, STN, and C∶N ratio in the Torreya. grandis cv. Merrillii region. The results showed that the average ω（SOC）, ω（STN）, and C∶N ratio were 17.63 g·kg-1, 1.48 g·kg-1, and 12.65, respectively, and their coefficients of variation were 68.08%, 67.41%, and 46.03%, respectively, indicating a moderate degree of variability. In general, the SOC, STN, and C∶N ratio of the Torreya grandis cv. Merrillii plantations were at an intermediate level in the national plantation. The semi-variance results showed that the nugget/sill values of SOC, STN, and C∶N ratio were 49.98%, 45.88%, and 49.93%, respectively, demonstrating a moderate level of spatial autocorrelation. The spatial distribution results showed that SOC, STN, and C∶N ratio decreased from northeast to southwest, with the majority of the region exhibiting above-medium fertility levels of SOC. The results of correlation analysis and redundancy analysis indicated that AN, AP, and AK were significantly correlated with both SOC, STN, and C∶N ratio （P<0.05）. The results of random forest, structural equation model, and variation partitioning analysis evidenced that the main influencing factors of SOC and STN were soil-available nutrients （AN, AP, and AK）. Therefore, our results could provide important insights for enhancing soil carbon and nitrogen pools in special plantations in Zhejiang Province, enhancing the capacity of plantations to adapt to regional climate change through ecological measures such as appropriate fertilization practices and strategic understory vegetation cultivation.

Rapid and direct detection of m6A methylation by DNAzyme-based and smartphone-assisted electrochemical biosensor.

m6A methylation detection is crucial for understanding RNA functions, revealing disease mechanisms, guiding drug development and advancing epigenetics research. Nevertheless, high-throughput sequencing and liquid chromatography-based traditional methods still face challenges to rapid and direct detection of m6A methylation. Here we report a DNAzyme-based and smartphone-assisted electrochemical biosensor for rapid detection of m6A. We initially identified m6A methylation-sensitive DNAzyme mutants through site mutation screening. These mutants were then combined with tetrahedral DNA to modify the electrodes, creating a 3D sensing interface. The detection of m6A was accomplished by using DNAzyme to capture and cleave the m6A sequence. The electrochemical biosensor detected the m6A sequence at nanomolar concentrations with a low detection limit of 0.69 nM and a wide detection range from 10 to 104 nM within 60 min. As a proof of concept, the 3'-UTR sequence of rice was selected as the m6A analyte. Combined with a smartphone, our biosensor shows good specificity, sensitivity, and easy-to-perform features, which indicates great prospects in the field of RNA modification detection and epigenetic analysis.

[Chemical constituents from stem bark of Aquilaria sinensis and their antibacterial activity against Helicobacter pylori].

The stem bark of Aquilaria sinensis(Thymelaeaceae), with the local name of "Li-Wa-Zi-Xing", is used in traditional Yi medicine for treating chronic gastritis and other diseases. However, its active ingredients remain currently unknown. In this study, Helicobacter pylori(Hp) is used in anti-bacterial experiments to test the active compounds derived from A. sinensis stem bark. Nineteen compounds were isolated from the stem bark of A. sinensis by column chromatography, high-performance liquid chromatography, recrystallization, etc. Aquilaridiester(1) is a new lignan. The other eighteen compounds were reported before, including docosyl caffeate(2), 6-hydroxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(3), qinanone A(4), 6-hydroxy-2-(2-phenylethyl)chromone(5), 6-hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(6), 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-1-benzopyran-4-one(7), 6-hydroxy-2-[2-(3,4-dimethoxyphenyl)ethyl]chromone(8), 6-hydroxy-2-[(1E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-4H-1-benzopyran-4-one(9), genkwanin(10), 5-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one(11), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(12),(+)-syringaresinol(13), zhebeiresinol(14), aquilarin A(15), caruilignan D(16),(-)-ficusal(17), pistaciamide(18), and protocatechuic acid(19). The anti-bacterial results show that compounds 2-7, 10-11, and 13 have inhibitory activity against Hp. Among them, 6-hydroxy-2-(2-phenylethyl)chromone(5) and 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-benzopyran-4-one(7) have superior inhibitory effects on Hp to others, with the same minimum inhibitory concentration(MIC) of 6.25 µmol·L~(-1). The 2-(2-phenylethyl)chromones are the major active ingredients in A. sinensis stem bark.

Belzutifan for patients with von Hippel-Lindau disease-associated CNS haemangioblastomas (LITESPARK-004): a multicentre, single-arm, phase 2 study.

BACKGROUND: The first-in-class hypoxia-inducible factor-2α inhibitor, belzutifan, showed clinically meaningful antitumour activity in von Hippel-Lindau (VHL) disease-associated neoplasms in the ongoing, single-arm, phase 2 LITESPARK-004 study. We aimed to investigate antitumour activity with an additional 16 months of follow-up and present updated results for the subgroup of patients with CNS haemangioblastomas. METHODS: In the multicentre, single-arm, phase 2 LITESPARK-004 study, adults (aged ≥18 years) from 11 cancer centres or hospitals in the USA, Denmark, France, and the UK, with germline VHL alterations, at least one measurable renal cell carcinoma tumour, no renal cell carcinoma tumour greater than 3 cm requiring immediate surgical intervention, an Eastern Cooperative Oncology Group performance status 0 or 1, and no previous systemic therapy received oral belzutifan 120 mg once daily until unacceptable toxicity, disease progression, or patient decision to withdraw. The primary endpoint, evaluated in patients with CNS haemangioblastomas, was the proportion of patients with an objective response per RECIST version 1.1 by an independent review committee. We assessed response using two approaches. In approach 1, we evaluated all measurable (≥1 cm maximum diameter) or non-measurable lesions at baseline, including both the solid lesion and the associated cystic component if present. In approach 2, we evaluated only baseline lesions with a measurable (≥1 cm maximum diameter) solid lesion. Antitumour activity was assessed in all patients who received at least one dose of belzutifan. This study is no longer recruiting but is ongoing, and is registered with Clinicaltrials.gov, NCT03401788. FINDINGS: Between May 31, 2018, and March 29, 2019, of 67 patients screened, 61 (32 [52%] male and 29 [48%] female) were enrolled; 50 (82%) had at least one CNS haemangioblastoma evaluable at baseline (184 total lesions). Median follow-up for the 50 patients with CNS haemangioblastomas was 38·0 months (IQR 36·7-40·1). In approach 1, 22 of 50 patients (44% [95% CI 30-59]) had an objective response. In approach 2, 19 of 25 patients (76% [55-91] had an objective response. 23 (46%) of 50 patients had a grade 3-5 all-cause adverse event. 19 (38%) patients reported grade 3 adverse events, the most common of which was anaemia (in 6 [12%] patients). Two of 50 patients (4%) reported grade 4 events (retinal vein occlusion and embolism). Two patients died owing to adverse events not considered treatment-related (suicide and toxicity to various agents). INTERPRETATION: Belzutifan showed meaningful antitumour activity in VHL disease-associated CNS haemangioblastomas that was sustained for more than 3 years of treatment. These results continue to support belzutifan as a systemic treatment option for patients with VHL disease-related CNS haemangioblastomas. FUNDING: Merck Sharp & Dohme, National Institutes of Health, and National Cancer Institute.