Induction of Petite Colonies in Candida glabrate via Rose Bengal-Mediated Photodynamic Therapy.

Facing a 40% mortality rate in candidemia patients, drug-resistant Candida and their petite mutants remain a major treatment challenge. Antimicrobial photodynamic therapy (aPDT) targets multiple fungal structures, unlike antibiotics/antifungals, potentially thwarting resistance. Traditional methods for inducing petite colonies rely on ethidium bromide or fluconazole, which can influence drug susceptibility and stress responses. This study investigated the application of green light (peak 520 nm) and rose bengal (RB) photosensitizer to combat a drug-resistant Candida glabrata isolate. The findings revealed that aPDT treatment significantly inhibited cell growth (≥99.9% reduction) and effectively induced petite colony formation, as evidenced by reduced size and loss of mitochondrial redox indicator staining. This study provides initial evidence that aPDT can induce petite colonies in a multidrug-resistant C. glabrata strain in vitro, offering a potentially transformative approach for combating resistant fungal infections.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Boosting 2000-Fold Hypergolic Ignition Rate of Carborane by Substitutes Migration in Metal Clusters.

Hypergolic propellants rely on fuel and oxidizer that spontaneously ignite upon contact, which fulfill a wide variety of mission roles in launch vehicles and spacecraft. Energy-rich carboranes are promising hypergolic fuels, but triggering their energy release is quite difficult because of their ultrastable aromatic cage structure. To steer the development of carborane-based high-performance hypergolic material, carboranylthiolated compounds integrated with atomically precise copper clusters are presented, yielding two distinct isomers, Cu14B-S and Cu14C-S, both possessing similar ligands and core structures. With the migration of thiolate groups from carbon atoms to boron atoms, the ignition delay (ID) time shortened from 6870 to 3 ms when contacted with environmentally benign oxidizer high-test peroxide (HTP, with a H2O2 concentration of 90%). The extraordinarily short ignition ID time of Cu14B-S is ranking among the best of HTP-active hypergolic materials. The experimental and theoretical findings reveal that benefitting from the migration of thiolate groups, Cu14B-S, characterized by an electron-rich metal kernel, displays enhanced reducibility and superior charge transfer efficiency. This results in exceptional activation rates with HTP, consequently inducing carborane combustion and the simultaneous release of energy. This fundamental investigation shed light on the development of advanced green hypergolic propulsion systems.

Vertically Concentrated Quantum Wells Enabling Highly Efficient Deep-Blue Perovskite Light-Emitting Diodes.

Deep-blue perovskite light-emitting diodes (PeLEDs) based on quasi-two-dimensional (quasi-2D) systems exist heightened sensitivity to the domain distribution. The top-down crystallization mode will lead to a vertical gradient distribution of quantum well (QW) structure, which is unfavorable for deep-blue emission. Herein, a thermal gradient annealing treatment is proposed to address the polydispersity issue of vertical QWs in quasi-2D perovskites. The formation of large-n domains at the upper interface of the perovskite film can be effectively inhibited by introducing a low-temperature source in the annealing process. Combined with the utilization of NaBr to inhibit the undesirable n=1 domain, a vertically concentrated QW structure is ultimately attained. As a result, the fabricated device delivers a narrow and stable deep-blue emission at 458 nm with an impressive external quantum efficiency (EQE) of 5.82%. Green and sky-blue PeLEDs with remarkable EQE of 21.83% and 17.51% are also successfully achieved, respectively, by using the same strategy. The findings provide a universal strategy across the entire quasi-2D perovskites, paving the way for future practical application of PeLEDs.

Complete Mitogenome sequencing of the fish louse Argulus japonicus (Crustacea: Branchiura): Comparative analyses and phylogenetic implications.

The fish louse Argulus japonicus, a branchiuran crustacean of the Argulidae family, is attracting increasing attention because of its parasitic tendencies and significant health threats to global fish farming. The mitogenomes can yield a foundation for studying epidemiology, genetic diversity, and molecular ecology and therefore may be used to assist in the surveillance and control of A. japonicus. In this study, we sequenced and assembled the complete mitogenome of A. japonicus to shed light on its genetic and evolutionary blueprint. Our investigation indicated that the 15,045-bp circular genome of A. japonicus encodes 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and 2 ribosomal RNAs (rRNAs) with significant AT and GC skews. Comparative genomics provided an evolutionary scenario for the genetic diversity of 13 PCGs: all were under purifying selection, with cox1 and nad6 having the lowest and highest evolutionary rates, respectively. Genome-wide phylogenetic trees established a close relationship between species of the families Argulidae (Arguloida) and Armilliferidae (Porocephalida) within Crustacea, and further, A. japonicus and Argulus americanus were determined to be more closely related to each other than to others within the family Argulidae. Single PCG-based phylogenies supported nad1 and nad6 as the best genetic markers for evolutionary and phylogenetic studies for branchiuran crustaceans due to their similar phylogenetic topologies with those of genome-based phylogenetic analyses. To sum up, these comprehensive mitogenomic data of A. japonicus and related species refine valuable marker resources and should contribute to molecular diagnostic methods, epidemiological investigations, and ecological studies of the fish ectoparasites in Crustacea.

Impact of Viloxazine Extended-Release Capsules (Qelbree®) on Select Cytochrome P450 Enzyme Activity and Evaluation of CYP2D6 Genetic Polymorphisms on Viloxazine Pharmacokinetics.

BACKGROUND AND OBJECTIVE: Viloxazine extended-release (ER) [Qelbree®] is a nonstimulant attention-deficit/hyperactivity disorder (ADHD) treatment. In vitro studies suggested potential for viloxazine to inhibit cytochrome 450 (CYP) enzymes 1A2, 2B6, 2D6 and 3A4. This clinical study therefore evaluated viloxazine ER effects on index substrates for CYP1A2, 2D6, and 3A4, and secondarily evaluated the impact of CYP2D6 polymorphisms on viloxazine pharmacokinetics. METHODS: Thirty-seven healthy subjects received a modified Cooperstown cocktail (MCC; caffeine 200 mg, dextromethorphan 30 mg, midazolam 0.025 mg/kg) on Day 1, viloxazine ER 900 mg/day on Days 3-5, and a combination of viloxazine ER 900 mg and MCC on Day 6. Viloxazine ER effects on MCC substrates were evaluated using analysis of variance. The impact of CYP2D6 genetic polymorphisms on steady-state viloxazine plasma concentrations was evaluated using Student's t test assessing pharmacokinetic parameter differences between poor versus extensive metabolizers. RESULTS: The least squares geometric mean ratio [GMR%] (90% CI) of MCC substrate + viloxazine ER/MCC substrate alone for caffeine maximum concentration (Cmax), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUCt), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC∞) was 99.11 (95.84-102.49), 436.15 (398.87-476.92), and 583.35 (262.41-1296.80), respectively; 150.76 (126.03-180.35), 185.76 (155.01-222.61), and 189.71 (160.37-224.42) for dextromethorphan Cmax, AUCt, and AUC∞, respectively; and 112.81 (104.71-121.54), 167.56 (153.05-183.45), and 168.91 (154.38-184.80) for midazolam Cmax, AUCt, and AUC∞, respectively. At steady state, viloxazine least squares GMR (90% CI) for poor/extensive CYP2D6 metabolizers were Cmax 120.70 (102.33-142.37) and area under the plasme concentration-time curve from time 0 to 24 hours (AUC0-24 125.66 (105.36-149.87)). CONCLUSION: Viloxazine ER is a strong CYP1A2 inhibitor and a weak CYP2D6 and CYP3A4 inhibitor. CYP2D6 polymorphisms did not meaningfully alter the viloxazine ER pharmacokinetic profile.

Clinical efficacy of precision liver resection for primary liver cancer.

AIM: Precision liver resection is considered the gold standard in liver surgery. Therefore, optimizing the resection of lesions and minimizing unnecessary time of liver ischemia and hypoxia have become focal points. METHODS: A total of 96 patients with primary liver cancer admitted to Cangzhou People's Hospital from January 2017 and December 2019 were included in this retrospective study, and divided into two groups according to the different surgical treatment, with 50 cases in the control group (conventional hepatic resection) and 46 cases in the observation group (precision liver resection). The surgical indicators, liver function, alpha-fetoprotein (AFP), complications, and three-year follow-up results were analyzed in the two groups. RESULTS: The operation time, intraoperative bleeding, hospital stay, and time of anal venting in the observation group were shorter than those in the control group (P<0.05). One week after surgery, AST, TBiL, ALT, and γ-GT levels decreased in both groups, with more significant decreases in the observation group than those in the control group (P<0.05). PCT and hs-CRP levels in the observation group were significantly lower than those in the control group (P<0.05) observation. The incidences of pleural effusion, bile leak, abdominal infection, pulmonary infection, as well as the total complication rates in the observation group were lower in the observation group than those in the control group (P<0.05). The follow-up data revealed that the observation group exhibited a lower recurrence rate observationand higher survival rate than the control group within 3 years, but these differences were not significant (P>0.05). CONCLUSION: Precision liver resection can effectively treat primary liver cancer, reduce the incidence of complications, and promote patient recovery after surgery.

Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression.

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. METHODS: Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. RESULTS: Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0-C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. CONCLUSIONS: The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.

Full-length αIIbß3 cryo-EM structure reveals intact integrin initiate-activation intrinsic architecture.

Integrin αIIbß3 is the key receptor regulating platelet retraction and accumulation and a proven drug-target for antithrombotic therapies. Here we resolve the cryo-EM structures of the full-length αIIbß3, which covers three distinct states along the activation pathway. Firstly, we obtain the αIIbß3 structure at 3 Å resolution in the inactive state, revealing the overall topology of the heterodimer with the transmembrane (TM) helices and the ligand-binding domain tucked in a specific angle proximity to the TM region. After the addition of a Mn2+ agonist, we resolve two coexisting structures representing two new states between inactive and active state. Our structures show conformational changes of the αIIbß3 activating trajectory and a unique twisting of the integrin legs, which is required for platelets accumulation. Our structure provides direct structural evidence for how the lower legs are involved in full-length integrin activation mechanisms and offers a new strategy to target the αIIbß3 lower leg.

ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the resistance to AR targeted therapies in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity.

Structure optimizing of flavonoids against both MRSA and VRE.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.

Preoperative oral hygiene treatment reduces bacterial transport and colonization during intubation for orthopedic surgery.

PURPOSE: The process of infection by bacteria and viruses involves invasion, establishment, growth, and parasitization. Poor oral hygiene and dysbiosis are significant risk factors for pneumonia. The aim of this study was to evaluate bacterial transport into the trachea during intubation for orthopedic surgery and the impact of oral hygiene treatment. METHODS: The study cohort included 53 patients with fracture who underwent surgical procedures under general anesthesia and were divided into two groups: an oral hygiene treatment (OHT) group (n = 27) and a control group (n = 26). Before intubation, the OHT group underwent preoperative oral hygiene treatment. Microbiological culture was used for detection and counting of bacteria from the oropharynx, trachea, and tip of the endotracheal tube (ETT). RESULTS: Patients in the OHT group had a lower pathogen detection rate and lower degree of bacterial colonization in the oropharynx, trachea, and ETT tip. CONCLUSION: Preoperative oral hygiene treatment is able to reduce bacterial transport and colonization during orthopedic surgery, thus providing an important adjunct to pre-anesthesia care.

Large-scale research on durability test cycle of fuel cell system based on CATC.

Durability is one of the technical bottlenecks restricting fuel cell electric vehicle development. As a result, significant time and resources have been invested in research related to this area worldwide. Current durability research mainly focuses on the single cell and stack levels, which is quite different from the usage scenarios of actual vehicles. There is almost no research on developing durability test cycles on the fuel cell system level. This paper proposes a universal model for developing a durability test cycle for fuel cell system based on the China automotive test cycle. Large-scale comparison tests of the fuel cell systems are conducted. After 1000 h test, the output performance degradation of three mass-produced fuel cell system is 14.49%, 9.59%, and 4.21%, respectively. The test results show that the durability test cycle proposed in this paper can effectively accelerate the durability test of the fuel cell system and evaluate the durability performance of the fuel cell system. Moreover, the methodology proposed in this paper could be used in any other test cycles such as NEDC (New European Driving Cycle), WLTC (Worldwide Harmonized Light Vehicles Test Procedure), etc. And it has comprehensive application value and are significant for reducing the cost of durability testing of fuel cell systems and promoting the industrialization of fuel cell electric vehicles.

Interfacial Enhancement and Composite Manufacturing of Continuous Carbon-Fiber-Reinforced PA6T Composites via PrePA6T Ultrafine Powder.

Semi-aromatic poly (hexamethylene terephthalamide) (PA6T) oligomer (prePA6T) ultrafine powder, with a diameter of <5 µm, was prepared as an emulsion sizing agent to improve the impregnation performance of CF/PA6T composites. The prePA6T hyperfine powder was acquired via the dissolution and precipitation "phase conversion" method, and the prePA6T emulsion sizing agent was acquired to continuously coat the CF bundle. The sized CF unidirectional tape was knitted into a fabric using the plain weave method, while the CF/PA6T laminated composites were obtained by laminating the plain weave fabrics with PA6T films. The interfacial shear strength (IFSS), tensile strength (TS), and interlaminar shear strength (ILSS) of prePA6T-modified CF/PA6T composites improved by 54.9%, 125.3%, and 120.9%, respectively. Compared with the commercial polyamide sizing agent product PA845H, the prePA6T sizing agent showed better interfacial properties at elevated temperatures, especially no TS loss at 75 °C. The SEM observations also indicated that the prePA6T emulsion has an excellent impregnation effect on CF, and the fracture mechanism shifted from adhesive failure mode to cohesive failure mode. In summary, a facile, heat-resistant, undamaged-to-fiber environmental coating process is proposed to continuously manufacture high-performance thermoplastic composites, which is quite promising in mass production.

A von-Neumann-like photonic processor and its application in studying quantum signature of chaos.

Photonic quantum computation plays an important role and offers unique advantages. Two decades after the milestone work of Knill-Laflamme-Milburn, various architectures of photonic processors have been proposed, and quantum advantage over classical computers has also been demonstrated. It is now the opportune time to apply this technology to real-world applications. However, at current technology level, this aim is restricted by either programmability in bulk optics or loss in integrated optics for the existing architectures of processors, for which the resource cost is also a problem. Here we present a von-Neumann-like architecture based on temporal-mode encoding and looped structure on table, which is capable of multimode-universal programmability, resource-efficiency, phase-stability and software-scalability. In order to illustrate these merits, we execute two different programs with varying resource requirements on the same processor, to investigate quantum signature of chaos from two aspects: the signature behaviors exhibited in phase space (13 modes), and the Fermi golden rule which has not been experimentally studied in quantitative way before (26 modes). The maximal program contains an optical interferometer network with 1694 freely-adjustable phases. Considering current state-of-the-art, our architecture stands as the most promising candidate for real-world applications.

RNAirport: a deep neural network-based database characterizing representative gene models in plants.

A 5'-leader, known initially as the 5'-untranslated region, contains multiple isoforms due to alternative splicings (aS) and transcription start sites (aTSS). Therefore, a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency. Here, we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species. We rank the intra- and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader. To further assign a representative 5'-end, we train the deep-learning model 5'leaderP to learn aTSS-mediated 5'-end distribution patterns from cap-analysis gene expression (CAGE) data. The model accurately predicts the 5'-end, confirmed experimentally in Arabidopsis and rice. The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport (http://www.rnairport.com/leader5P/). This stage 1 5'-leader annotation records 5'-leader diversity and will pave the way to Ribo-Seq ORF annotation, identical to the project recently initiated by human GENCODE.

Evaluating Prognosis of Gastrointestinal Metastatic Neuroendocrine Tumors: Constructing a Novel Prognostic Nomogram Based on NETPET Score and Metabolic Parameters from PET/CT Imaging.

INTRODUCTION: The goal of this study is to compare the prognostic performance of NETPET scores, based on gallium-68 DOTANOC (68Ga-DOTANOC) and fluorine-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography-Computed Tomography (PET-CT), and PET-CT metabolic parameters in metastatic gastrointestinal neuroendocrine tumors (GI-NET), while constructing and validating a nomogram derived from dual-scan PET-CT. METHODS: In this retrospective study, G1-G3 GI-NET patients who underwent 68Ga-DOTANOC and 18F-FDG PET scans were enrolled and divided into training and internal validation cohorts. Three grading systems were constructed based on NETPET scores and standardized uptake value maximum (SUVmax). LASSO regression selected variables for a multivariable Cox model, and nomograms predicting progression-free survival (PFS) and overall survival (OS) were created. The prognostic performance of these systems was assessed using time-dependent receiver-operating characteristic (ROC) curves, concordance index (C-index), and other methods. Nomogram evaluation involved calibration curves, decision curve analysis (DCA), and the aforementioned methods in both cohorts. RESULTS: In this study, 223 patients (130 males; mean age ± SD: 52.6 ± 12 years) were divided into training (148) and internal validation (75) cohorts. Dual scans were classified based on NETPET scores (D1-D3). Single 68Ga-DOTANOC and 18F-FDG PET-CT scans were stratified into S1-S3 and F1-F3 based on SUVmax. The NETPET score-based grading system demonstrated the best OS and PFS prediction (C-index, 0.763 vs. 0.727 vs. 0.566). Nomograms for OS and PFS exhibited superior prognostic performance in both cohorts (all AUCs > 0.8). CONCLUSIONS: New classification based on NETPET score predicts patient OS/PFS best. PET-CT-based nomograms show accurate OS/PFS forecasts.

Cyclooctatetraene-Embedded Carbon Nanorings.

With the prosperity of the development of carbon nanorings, certain topologically or functionally unique units-embedded carbon nanorings have sprung up in the past decade. Herein, we report the facile and efficient synthesis of three cyclooctatetraene-embedded carbon nanorings (COTCNRs) that contain three (COTCNR1 and COTCNR2) and four (COTCNR3) COT units in a one-pot Yamamoto coupling. These nano rings feature hoop-shaped segments of Gyroid (G-), Diamond (D-), and Primitive (P-) type carbon schwarzites. The conformations of the trimeric nano rings COTCNR1 and COTCNR2 are shape-persistent, whereas the tetrameric COTCNR3 possesses a flexible carbon skeleton which undergoes conformational changes upon forming host-guest complexes with fullerenes (C60 and C70), whose co-crystals may potentially serve as fullerene-based semiconducting supramolecular wires with the electrical conductivities on the order of 10-7 S cm-1 (for C60⊂COTCNR3) and 10-8 S cm-1 (for C70⊂COTCNR3) under ambient conditions. This research not only describes highly efficient one-step syntheses to three cyclooctatetraene-embedded carbon nanorings which feature hoop-shaped segments of distinctive topological carbon schwarzites, but also demonstrates the potential application of the one dimensional fullerenes array secured by COTCNR3 in electronics.