Search

Purpose: Gastric cancer (GC), one of the most prevalent and deadliest tumors worldwide, is often diagnosed at an advanced stage with limited treatment options and poor prognosis. The development of a CLDN18.2-targeted radioimmunotherapy probe is a potential treatment option for GC. Methods: The CLDN18.2 antibody TST001 (provided by Transcenta) was conjugated with DOTA and radiolabeled with the radioactive nuclide 177Lu. The specificity and targeting ability were evaluated by cell uptake, imaging and biodistribution experiments. In BGC823CLDN18.2/AGSCLDN18.2 mouse models, the efficacy of [177Lu]Lu-TST001 against CLDN18.2-expressing tumors was demonstrated, and toxicity was evaluated by H&E staining and blood sample testing. Results: [177Lu]Lu-TST001 was labeled with an 99.17%±0.32 radiochemical purity, an 18.50 ± 1.27 MBq/nmol specific activity and a stability of ≥ 94% after 7 days. It exhibited specific and high tumor uptake in CLDN18.2-positive xenografts of GC mouse models. Survival studies in BGC823CLDN18.2 and AGSCLDN18.2 tumor-bearing mouse models indicated that a low dose of 5.55 MBq and a high dose of 11.10 MBq [177Lu]Lu-TST001 significantly inhibited tumor growth compared to the saline control group, with the 11.1 MBq group showing better therapeutic efficacy. Histological staining with hematoxylin and eosin (H&E) and Ki67 immunohistochemistry of residual tissues confirmed tumor tissue destruction and reduced tumor cell proliferation following treatment. H&E showed that there was no significant short-term toxicity observed in the heart, spleen, stomach or other important organs when treated with a high dose of [177Lu]Lu-TST001, and no apparent hematotoxicity or liver toxicity was observed. Conclusion: In preclinical studies, [177Lu]Lu-TST001 demonstrated significant antitumor efficacy with acceptable toxicity. It exhibits strong potential for clinical translation, providing a new promising treatment option for CLDN18.2-overexpressing tumors, including GC. [ABSTRACT FROM AUTHOR]

Dynamic covalent bonds (DCBs) have attracted huge interest in the past two decades, particularly in polymer materials, due to their reversibility. The introduction of DCBs into polymers often endows the polymers with unprecedented properties such as self‐healing, shape memory, enhanced mechanical strength, and stimuli responsiveness. Specifically, DCBs offer unique opportunities for self‐healing materials by enabling the spontaneous reformation of covalent linkages and restoring structural integrity upon damaged or mechanical stress. Additionally, shape memory behavior allows polymers to retain programmed shapes and undergo reversible transformations triggered by external stimuli. This property finds applications in various fields such as biomedical devices and smart textiles. Furthermore, DCBs enhance mechanical strength, making polymers resilient and durable, thus expanding their applications in structural materials. Their stimuli responsiveness allows for dynamic modulation of properties based on environmental triggers, enabling the development of intelligent materials for sensors, drug delivery systems, and responsive coatings. This review provides an overview of commonly employed DCBs in polymer materials, explaining their dynamic behaviors, reversibility, and stabilities. It also explores the diverse applications of DCB‐based polymers, from self‐healing coatings to shape memory polymers. Through these advancements, the potential for future breakthroughs in materials science becomes evident. [ABSTRACT FROM AUTHOR]

Purpose: An accurate diagnosis of colorectal carcinoma (CRC) can assist physicians in developing reasonable therapeutic regimens, thereby significantly improving the patient's prognosis. Carcinoembryonic antigen (CEA)-targeted PET imaging shows great potential for this purpose. Despite showing remarkable abilities to detect primary and metastatic CRC, previously reported CEA-specific antibody radiotracers or pretargeted imaging are not suitable for clinical use due to poor pharmacokinetics and complicated imaging procedures. In contrast, radiolabeled nanobodies exhibit ideal characteristics for PET imaging, for instance, rapid clearance rates and excellent distribution profiles, allowing same-day imaging with sufficient contrast. In this study, we developed a novel CEA-targeted nanobody radiotracer, [68 Ga]Ga-HNI01, and assessed its tumor imaging ability and biodistribution profile in preclinical xenografts and patients with primary and metastatic CRC. Methods: The novel nanobody HNI01 was acquired by immunizing the llama with CEA proteins. [68 Ga]Ga-HNI01 was synthesized by site-specifically conjugating [68 Ga]Ga with tris(hydroxypyridinone) (THP). Small-animal PET imaging and biodistribution studies were performed in CEA-overexpressed LS174T and CEA-low-expressed HT-29 tumor models. Following successful preclinical assessment, a phase I study was conducted on 9 patients with primary and metastatic CRC. Study participants received 151.21 ± 25.25 MBq of intravenous [68 Ga]Ga-HNI01 and underwent PET/CT scans at 1 h and 2 h post injection. Patients 01–03 also underwent whole-body dynamic PET imaging within 0–40 min p.i. All patients underwent [18F]F-FDG PET/CT imaging within 1 week after [68 Ga]Ga-HNI01 imaging. Tracer distribution, pharmacokinetics, and radiation dosimetry were calculated. Results: [68 Ga]Ga-HNI01 was successfully synthesized within 10 min under mild conditions, and the radiochemical purity was more than 98% without purification. Micro-PET imaging with [68 Ga]Ga-HNI01 revealed clear visualization of LS174T tumors, while signals from HT-29 tumors were significantly lower. Biodistribution studies indicated that uptake of [68 Ga]Ga-HNI01 in LS174T and HT-29 was 8.83 ± 3.02%ID/g and 1.81 ± 0.87%ID/g, respectively, at 2 h p.i. No adverse events occurred in all clinical participants after the injection of [68 Ga]Ga-HNI01. A fast blood clearance and low background uptake were observed, and CRC lesions could be visualized with high contrast as early as 30 min after injection. [68 Ga]Ga-HNI01 PET could clearly detect metastatic lesions in the liver, lung, and pancreas and showed superior ability in detecting small metastases. A significant accumulation of radioactivity was observed in the kidney, and normal tissues physiologically expressing CEA receptors showed slight uptakes of [68 Ga]Ga-HNI01. An interesting finding was that strong uptake of [68 Ga]Ga-HNI01 was found in non-malignant colorectal tissues adjacent to the primary tumor in some patients, suggesting abnormal CEA expression in these healthy tissues. Conclusion: [68 Ga]Ga-HNI01 is a novel CEA-targeted PET imaging radiotracer with excellent pharmacokinetics and favorable dosimetry profiles. [68 Ga]Ga-HNI01 PET is an effective and convenient imaging tool for detecting CRC lesions, particularly for identifying small metastases. Furthermore, its high specificity for CEA in vivo makes it an ideal tool for selecting patients for anti-CEA therapy. [ABSTRACT FROM AUTHOR]

Photopolymerization has attracted great interest because of its mild reaction conditions, spatiotemporal controllability, cost efficiency, and fast speed. However, with the raising environmental awareness and the increasing attention to life and health, the leachability of photoinitiators has become a growing concern. In this research, a methacrylate functionalized triazine-based polymerizable visible light photoinitiator, 2-(((4-(2-(4,6-bis(trichloromethyl)-1,3,5-triazin-2-yl)vinyl)phenoxy)carbonyl)amino)ethyl methacrylate (CT) and its reversible addition–fragmentation chain transfer (RAFT) polymerized CT (pCT) were designed as the polymerizable and polymeric photoinitiators, respectively. The photoinitiation abilities of the investigated triazine derivatives were evaluated under violet LEDs. Due to the steric effect, pCT showed slightly reduced photoinitiation ability under both LED at 400 nm and 410 nm irradiation. Nevertheless, photopolymers initiated using CT and pCT showed excellent migration stability compared to those prepared by 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine (MT) and 4-(2-(4,6-bis(trichloromethyl)-1,3,5-triazin-2-yl)vinyl)phenol (PT). Specifically, CT and pCT-based polymers prepared under the irradiation of LED at 400 nm exhibited only 1/3-fold and 1/14-fold of photoinitiators leachability, while 1/2-fold and 1/6-fold of photoinitiator leachability were obtained compared to the MT-based photocured polymers when using LED at 410 nm. The excellent migration stability of pCT reveals potential applications in the biomedical and food packaging fields. [ABSTRACT FROM AUTHOR]

Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance. Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics. Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2–6%, 0.8–2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics. Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically. [ABSTRACT FROM AUTHOR]

Aims. To explore the effects of Biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway and to explore the possible antifibrotic mechanisms of the drug. Material and Method. A rat model of hepatic fibrosis was established via CCl4 induction. Liver function and antioxidant indices were detected using commercial kits. Hematoxylin-eosin and Masson staining were used to detect pathological changes in hepatic tissues. ELISA was used to measure plasma TNF-α, IL-β, and IL-6 levels. RT-PCR was used to measure changes in TNF-α, IL-β, and IL-6 levels in hepatic tissues. Changes in p65, P-p65, Nrf2, and HO-1 protein expression were detected using western blotting. Results. In rats with hepatic fibrosis, Biejiaxiaozheng pills effectively improved liver function, alleviated fibrosis in hepatic tissues, and significantly reduced collagen accumulation. The pills significantly downregulated inflammatory cytokine expression in hepatic tissues by suppressing p65 phosphorylation and reduced plasma inflammatory cytokine levels to some extent. The pills upregulated Nrf2 and HO-1 expression in hepatic tissues, enhanced antioxidant potential, and upregulated plasma antioxidant levels. Conclusion. Biejiaxiaozheng pills improved hepatic fibrosis symptoms and lesions in rats, likely by inhibiting the NF-κB pathway and promoting the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Heating a droplet without contamination is desired for the emerging applications of microfluidic devices in life science and materials science, especially in the form of controllable temperature distribution. Microfluidic heaters using surface acoustic waves have been recently demonstrated, which highlights an urgent need for an insight into the detailed heating mechanism to guide the development of temperature regulation methodologies. Here, we show that the temperature field of a droplet on the path of a travelling wave can be regulated by modulating the heat source distribution and thermal conduction inside the target. We model the acoustothermal process of the droplet including the effects of electric dissipation, acoustic dissipation, and acoustic-induced steady flow. The electric–mechanical–acoustic coupling contributes to the dominant heat source, and we call it acoustic heat source. The nonlinear effects of incident waves generate acoustic vortexes with a velocity of up to 20 mm s−1, inducing forced convection inside the droplet to enhance heat transfer. The equilibrium temperature field of a droplet is determined by a synergy of dissipative acoustic attenuation and acoustic streaming. We demonstrate that the distribution of the acoustic heat source and the patterns of acoustic streaming can be modulated by fluid viscosity and droplet size. Various spatial combinations of the acoustic heat source and steady streaming make different temperature fields in the droplet. We also propose a phase diagram of the temperature distribution in the droplet. This methodology enables opportunities for temperature-related processing inside a droplet bioparticle carrier or microreactor. [ABSTRACT FROM AUTHOR]

Background: The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. Methods: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. Results: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. Conclusions: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide. [ABSTRACT FROM AUTHOR]

Considering environmental changes and the demand for more sustainable energy sources, stricter requirements have been placed on electrode materials for sodium and potassium‐ion batteries, which are expected to provide higher energy and power density while being affordable and sustainable. Vanadium sulfide‐based materials have emerged as intriguing contenders for the next generation of anode materials due to their high theoretical capacity, abundant reserves, and cost‐effectiveness. Despite these advantages, challenges such as limited cycle life and restricted ion diffusion coefficients continue to impede their effective application in sodium and potassium‐ion batteries. To overcome the limitations associated with electrochemical performance and circumvent bottlenecks imposed by the inherent properties of materials at the bulk scale, this review comprehensively summarizes and analyzes the crystal structures, modification strategies, and energy storage processes of vanadium sulfide‐based electrode materials for sodium and potassium‐ion batteries. The objective is to guide the development of high‐performance vanadium‐based sulfide electrode materials with refined morphologies and/or structures, employing environmentally friendly and cost‐efficient methods. Finally, future perspectives and research suggestions for vanadium sulfide‐based materials are presented to propel practical applications forward. [ABSTRACT FROM AUTHOR]

Purpose: Programmed cell death protein-1/ligand-1 (PD-1/L1) blockade has been a breakthrough in the treatment of patients with non-small cell lung cancer (NSCLC), but there is still a lack of effective methods to screen patients. Here we report a novel 68 Ga-labeled nanobody [68 Ga]Ga-THP-APN09 for PET imaging of PD-L1 status in mouse models and a first-in-human study in NSCLC patients. Methods: [68 Ga]Ga-THP-APN09 was prepared by site-specific radiolabeling, with no further purification. Cell uptake assays were completed in the human lung adenocarcinoma cell line A549, NSCLC cell line H1975 and human PD-L1 gene-transfected A549 cells (A549PD−L1). The imaging to image PD-L1 status and biodistribution were investigated in tumor-bearing mice of these three tumor cell types. The first-in-human clinical translational trial was registered as NCT05156515. The safety, radiation dosimetry, biodistribution, and correlations of tracer uptake with immunohistochemical staining and major pathologic response (MPR) were evaluated in NSCLC patients who underwent adjuvant immunotherapy combined with chemotherapy. Results: Radiosynthesis of [68 Ga]Ga-THP-APN09 was achieved at room temperature and a pH of 6.0–6.5 in 10 min with a high radiochemical yield (> 99%) and 13.9–27.8 GBq/μmol molar activity. The results of the cell uptake study reflected variable levels of surface PD-L1 expression observed by flow cytometry in the order A549PD−L1 > H1975 > A549. In small-animal PET/CT imaging, H1975 and A549PD−L1 tumors were clearly visualized in an 8.3:1 and 2.2:1 ratios over PD-L1-negative A549 tumors. Ex vivo biodistribution studies showed that tumor uptake was consistent with the PET results, with the highest A549PD−L1 being taken up the most (8.20 ± 0.87%ID/g), followed by H1975 (3.69 ± 0.50%ID/g) and A549 (0.90 ± 0.16%ID/g). Nine resectable NSCLC patients were enrolled in the clinical study. Uptake of [68 Ga]Ga-THP-APN09 was mainly observed in the kidneys and spleen, followed by low uptake in bone marrow. The radiation dose is within a reliable range. Tumor uptake was positively correlated with PD-L1 expression TPS (rs = 0.8763, P = 0.019). Tumor uptake of [68 Ga]Ga-THP-APN09 (SUVmax) in MPR patients was higher than that in non-MPR patients (median SUVmax 2.73 vs. 2.10, P = 0.036, determined with Mann–Whitney U-test). Conclusion: [68 Ga]Ga-THP-APN09 has the potential to be transformed into a kit-based radiotracer for rapid, simple, one-step, room temperature radiolabeling. The tracer can detect PD-L1 expression levels in tumors, and it may make it possibility to predict the response of PD-1 immunotherapy combined with chemotherapy. Confirmation in a large number of cases is needed. Trial registration: Clinical Trial (NCT05156515). Registered 12 December 2021. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Deep ultraviolet (UV) photodetectors have important applications in the industrial and military fields. However, little research has been reported on organic phototransistors (OPTs) in the deep ultraviolet range. Here, a novel organic semiconductor containing a small torsion angle and low π‐conjugation 2,2':5',2"‐terthiophene groups, oF‐PTTTP, is designed and synthesized, which exhibits high carrier mobility and unique deep ultraviolet response. Accordingly, an OPT based on oF‐PTTTP single crystal shows high responsivity to deep‐UV light. The photodetectors achieve high photoresponsivity (R) of 857 A/W and detectivity (D*) of 3.2×1015 Jones under 280 nm light illumination (only 95 nW·cm–2). To the best of our knowledge, 280 nm is the deepest detection wavelength reported for organic phototransistors and this work presents a new molecule design concept for organic phototransistors with deep‐UV detection. [ABSTRACT FROM AUTHOR]

The disordered chain arrangement of polymer dielectrics has complex both internal and external effects on system performance, which generally stimulates the weak acquisition and grain boundaries of vapor‐deposited organic small molecule films (VDOSMFs) with thermally activated charge transport. As a result, achieving "band‐like" transmission of VDOSMs on polymer dielectrics is attempting to prove to be a major challenge. Three types of bi‐polymer dielectrics are developed to modulate charge transport from thermally activated mode to "band‐like" transport at the interfacial level. The bottom consisting of a polyimide layer is critical to interfacial modulation, which shows the selectively binding capability with up‐dielectric layers to realize the modulation of charge transport, as corroborated by interface characterization and density functional‐based tight‐binding calculation. The findings provide an effective strategy for modulating the charge transport through polymer dielectric engineering and also recommend a podium to further comprehend the electrical characteristics of small molecules in organic thin‐film transistors. [ABSTRACT FROM AUTHOR]

Phase‐change semiconductor is one of the best candidates for designing nonvolatile memory, but it has never been realized in organic semiconductors until now. Here, a phase‐changeable and high‐mobility organic semiconductor (3,6‐DATT) is first synthesized. Benefiting from the introduction of electrostatic hydrogen bond (S···H), the molecular conformation of 3,6‐DATT crystals can be reversibly modulated by the electric field and ultraviolet irradiation. Through experimental and theoretical verification, the tiny difference in molecular conformation leads to crystalline polymorphisms and dramatically distinct charge transport properties, based on which a high‐performance organic phase‐change memory transistor (OPCMT) is constructed. The OPCMT exhibits a quick programming/erasing rate (about 3 s), long retention time (more than 2 h), and large memory window (i.e., large threshold voltage shift over 30 V). This work presents a new molecule design concept for organic semiconductors with reversible molecular conformation transition and opens a novel avenue for memory devices and other functional applications. [ABSTRACT FROM AUTHOR]

Purpose: [18F]AlF-RESCA was introduced as a core particularly useful for 18F-labeling of heat-sensitive biomolecules. However, no translational studies have been reported up to now. Herein, we reported the first-in-human evaluation of an 18F-labeled anti-HER2 nanobody MIRC213 as a PET radiotracer for imaging HER2-positive cancers. Methods: MIRC213 was produced by E. coli and conjugated with (±)-H3RESCA-Mal. [18F]AlF-RESCA-MIRC213 was prepared at room temperature. Its radiochemical purity and stability of were determined by radio-HPLC with the size-exclusion chromatographic column. Cell uptake was performed in NCI-N87 (HER2 +) and MCF-7 (HER2-) cells and the cell-binding affinity was verified in SK-OV-3 (HER2 +) cells. Small-animal PET/CT was performed using SK-OV-3, NCI-N87, and MCF-7 tumor-bearing mice at 30 min, 1 h, and 2 h post-injection. For blocking experiment, excess MIRC213 was co-injected with radiotracer. Biodistribution were performed on SKOV-3 and MCF-7 tumor-bearing mice at 2 h post-injection. For clinical study, PET/CT images were acquired at 2 h and 4 h after injection of [18F]AlF-RESCA-MIRC213 (1.85–3.7 MBq/kg) in six breast cancer patients (3 HER2-positive and 3 HER2-negative). All patients underwent [18F]-FDG PET/CT within a week for tissue selection purpose. Distribution and dosimetry were calculated. Standardized uptake values (SUV) were measured in tumors and normal organs. Results: MIRC213 was produced with > 95% purity and modified with RESCA to obtain RESCA-MIRC213. [18F]AlF-RESCA-MIRC213 was prepared within 20 min at room temperature with the radiochemical yield of 50.48 ± 7.6% and radiochemical purity of > 98% (n > 10), and remained stable in both PBS (88%) and 5% HSA (92%) after 6 h. The 2 h cellular uptake of [18F]AlF-RESCA-MIRC213 in NCI-N87 cells was 11.22 ± 0.60 AD%/105 cells. Its binding affinity Kd value was determined to be 1.23 ± 0.58 nM. Small-animal PET/CT with [18F]AlF-RESCA-MIRC213 can clearly differentiate SK-OV-3 and NCI-N87 tumors from MCF-7 tumors and background with a high uptake of 4.73 ± 1.18 ID%/g and substantially reduced to 1.70 ± 0.13 ID%/g for the blocking group (p < 0.05) in SK-OV-3 tumors at 2 h post-injection. No significant bone radioactivity was seen in the tumor-bearing animals. In all six breast cancer patients, there was no adverse reaction during study. The uptake of [18F]AlF-RESCA-MIRC213 was mainly in lacrimal gland, parotid gland, submandibular gland, thyroid gland, gallbladder, kidneys, liver, and intestines. There was no significant bone radioactivity accumulation in cancer patients. [18F]AlF-RESCA-MIRC213 had significantly higher tumor uptake in lesions from HER2-positive patients than that lesions from HER2-negative patients (SUVmax of 3.62 ± 1.56 vs. 1.41 ± 0.41, p = 0.0012) at 2 h post-injection. The kidneys received the highest radiation dose of 2.42 × 10−1 mGy/MBq, and the effective dose was 1.56 × 10−2 mSv/MBq. Conclusions: [18F]AlF-RESCA-MIRC213 could be prepared with high radiolabeling yield under mild conditions. [18F]AlF-RESCA-MIRC213 has relatively high stability both in vitro and in vivo. The results from clinical transformation suggest that [18F]AlF-RESCA-MIRC213 PET/CT is a safe procedure with favorable pharmacokinetics and dosimetry profile, and it is a promising new PET radiotracer for noninvasive diagnosis of HER2-positive cancers. [ABSTRACT FROM AUTHOR]

Organic semiconductors with combinative high carrier mobility and efficient solid‐state emission are full of challenges but urgently pursued for developing new emerging optoelectronics. Herein, by delicately regulating the crystal packing of an anthracene‐based molecular crystal via terminal tert‐butylation, we developed a superior high mobility emissive molecule, 2,6‐di(6‐tert‐butylnaphthyl)anthracene (TBU‐DNA). The unique "slipped herringbone" packing motif of TBU‐DNA enables its appropriate exciton‐exciton coupling and electron‐phonon coupling, thus resulting in remarkably high solid‐state emission (photoluminescence quantum yield, ΦF≈74.9 %) and efficacious charge transport (carrier mobility, μ=5.0 cm2 V−1 s−1). Furthermore, OLETs based on TBU‐DNA show an external quantum efficiency (EQE) of 1.8 %, which is among the highest EQE values for single component OLETs reported till now. This work presents a crystal engineering strategy via exquisite molecular design to realize high mobility emissive organic semiconductors. [ABSTRACT FROM AUTHOR]

Organic semiconductors with combinative high carrier mobility and efficient solid‐state emission are full of challenges but urgently pursued for developing new emerging optoelectronics. Herein, by delicately regulating the crystal packing of an anthracene‐based molecular crystal via terminal tert‐butylation, we developed a superior high mobility emissive molecule, 2,6‐di(6‐tert‐butylnaphthyl)anthracene (TBU‐DNA). The unique "slipped herringbone" packing motif of TBU‐DNA enables its appropriate exciton‐exciton coupling and electron‐phonon coupling, thus resulting in remarkably high solid‐state emission (photoluminescence quantum yield, ΦF≈74.9 %) and efficacious charge transport (carrier mobility, μ=5.0 cm2 V−1 s−1). Furthermore, OLETs based on TBU‐DNA show an external quantum efficiency (EQE) of 1.8 %, which is among the highest EQE values for single component OLETs reported till now. This work presents a crystal engineering strategy via exquisite molecular design to realize high mobility emissive organic semiconductors. [ABSTRACT FROM AUTHOR]

It is generally believed that the incorporation of fluorine functional groups into dielectrics can effectively impede the charge‐trapping process and improve carrier mobility. However, the relationship between the device performance and fluorinated groups is still not clear and also the modulation effect of fluorine functional groups on photogenerated charge carrier in phototransistors has not yet been investigated. Herein, phototransistors are constructed by using three kinds of gate dielectric layers with different fluorinated groups to exploit the effect of fluorine functional groups. It is concluded that the presence of fluorinated groups indeed increases the transistor mobility and optical figures of merit in phototransistors compared to the device with a fluorine‐free dielectric layer. Concurrently, the exciton binding energy is increased with the addition of fluorinated groups, resulting in the decrease of phototransistor performance compared with less content of fluorinated groups due to the synergistic balance effect of fluorine functional groups. The results further clarify how the fluorine functional groups optimize the interface of organic phototransistors and modulate the photoelectric performance. [ABSTRACT FROM AUTHOR]

Background: Cell‐free messenger RNA (cf‐mRNA) and long non‐coding RNA (cf‐lncRNA) are becoming increasingly important in liquid biopsy by providing biomarkers for disease prediction, diagnosis and prognosis, but the simultaneous characterization of coding and non‐coding RNAs in human biofluids remains challenging. Methods: Here, we developed polyadenylation ligation‐mediated sequencing (PALM‐Seq), an RNA sequencing strategy employing treatment of RNA with T4 polynucleotide kinase to generate cell‐free RNA (cfRNA) fragments with 5′ phosphate and 3′ hydroxyl and RNase H to deplete abundant RNAs, achieving simultaneous quantification and characterization of cfRNAs. Results: Using PALM‐Seq, we successfully identified well‐known differentially abundant mRNA, lncRNA and microRNA in the blood plasma of pregnant women. We further characterized cfRNAs in blood plasma, saliva, urine, seminal plasma and amniotic fluid and found that the detected numbers of different RNA biotypes varied with body fluids. The profiles of cf‐mRNA reflected the function of originated tissues, and immune cells significantly contributed RNA to blood plasma and saliva. Short fragments (<50 nt) of mRNA and lncRNA were major in biofluids, whereas seminal plasma and amniotic fluid tended to retain long RNA. Body fluids showed distinct preferences of pyrimidine at the 3′ end and adenine at the 5′ end of cf‐mRNA and cf‐lncRNA, which were correlated with the proportions of short fragments. Conclusion: Together, PALM‐Seq enables a simultaneous characterization of cf‐mRNA and cf‐lncRNA, contributing to elucidating the biology and promoting the application of cfRNAs. [ABSTRACT FROM AUTHOR]

Integrating high charge‐carrier mobility and low‐threshold lasing action in an organic semiconductor is crucial for the realization of an electrically pumped laser, but remains a great challenge. Herein, we present an organic semiconductor, named as 2,7‐di(2‐naphthyl)‐9H‐fluorene (LD‐2), which shows an unexpected high charge‐carrier mobility of 2.7 cm2 V−1 s−1 and low‐threshold lasing characteristic of 9.43 μJ cm−2 and 9.93 μJ cm−2 and high‐quality factor (Q) of 2131 and 1684 at emission peaks of 420 and 443 nm, respectively. Detailed theoretical calculations and photophysical data analysis demonstrate that a large intermolecular transfer integral of 10.36–45.16 meV together with a fast radiative transition rate of 8.0×108 s−1 are responsible for the achievement of the superior integrated optoelectronic properties in the LD‐2 crystal. These optoelectronic performances of LD‐2 are among the highest reported low‐threshold lasing organic semiconductors with efficient charge transport, suggesting its promise for research of electrically pumped organic lasers (EPOLs). [ABSTRACT FROM AUTHOR]

Integrating high charge‐carrier mobility and low‐threshold lasing action in an organic semiconductor is crucial for the realization of an electrically pumped laser, but remains a great challenge. Herein, we present an organic semiconductor, named as 2,7‐di(2‐naphthyl)‐9H‐fluorene (LD‐2), which shows an unexpected high charge‐carrier mobility of 2.7 cm2 V−1 s−1 and low‐threshold lasing characteristic of 9.43 μJ cm−2 and 9.93 μJ cm−2 and high‐quality factor (Q) of 2131 and 1684 at emission peaks of 420 and 443 nm, respectively. Detailed theoretical calculations and photophysical data analysis demonstrate that a large intermolecular transfer integral of 10.36–45.16 meV together with a fast radiative transition rate of 8.0×108 s−1 are responsible for the achievement of the superior integrated optoelectronic properties in the LD‐2 crystal. These optoelectronic performances of LD‐2 are among the highest reported low‐threshold lasing organic semiconductors with efficient charge transport, suggesting its promise for research of electrically pumped organic lasers (EPOLs). [ABSTRACT FROM AUTHOR]

Molecule design of organic semiconductors (OSCs) for eliminating photoresponse and maintaining high charge mobility concurrently is beneficial to realize intrinsically photostable and high‐performance organic field‐effect transistors (OFETs), which has never been reported. Here, a novel organic semiconductor TFP‐TT‐TPA with a centrosymmetric structure is synthesized. Remarkably, OFETs with TFP‐TT‐TPA show negligible photoresponse under light intensity up to 170.4 mW cm−2 (higher than sunlight intensity, about 138 mW cm−2), which ensures that the devices can work stably under sunlight. Through the single‐crystal structure and exciton dynamics analysis, it is found that the specific structure design can make strong intermolecular D–A interaction that occurs in the aggregate state, which facilitates the process of exciton quenching and thus enables the photostable OFETs. This study provides a new strategy for the design of organic semiconductors with intrinsic photostability and the construction of photostable organic optoelectronic devices for applications in light environment. [ABSTRACT FROM AUTHOR]

Purpose. M2-like tumor-associated macrophages (TAMs) are crucial component of immune infiltration in tumor microenvironment (TME), and exosomes derived from TAMs contributed to the regulation of tumor progression through cellular communication. However, in bladder cancer, the role of exosomal components still remains largely unknown. In the current study, we investigated the role of exosomes derived from M2-like TAMs in the regulation of autophagy in bladder cancer (BC) cells. Methods. THP-1 cells were stimulated with IL-4 and IL-13 for the polarization of TAMs, and exosomes were extracted by ultracentrifugation. H19 overexpression plasmid and H19 siRNAs were used in the study. Fluorescent analysis was performed for GFP-LC3 detection. Levels of autophagy and potential target were confirmed by western blot assay and immunoprecipitation. Results. We found that TAMs-exosome treatment significantly enhanced autophagy in BC cells, and the expression of lncRNA H19 was greatly upregulated in TAMs-exosome. Silencing of lncRNA H19 in TAMs-exo obviously decreased the levels of LC3-II expression whereas the p62 levels were increased. Mechanistically, silencing of exosomal H19 from TAMs alleviated ULK1 stabilization in BC cells through promoting K48-linked polyubiquitination of ULK1. At last, we found that overexpression of exosomal H19 from TAMs suppressed the interaction between ULK1 and its specific E3 ligase NEDD4L in BC cells. Conclusion. We revealed the effect of TAMs-exo-contained lncRNA H19 on regulating autophagy of bladder cancer cells, which indicated that targeting TAMs-H19 is a promising therapeutic strategy for the treatment of BC. [ABSTRACT FROM AUTHOR]

Purpose: Overexpression of epithelial cell adhesion molecule (EpCAM) plays essential roles in tumorigenesis and tumor progression in almost all epithelium-derived cancer. Monitoring EpCAM expression in tumors can be used for the diagnosis, staging, and prognosis of cancer patients, as well as guiding the individualized treatment of EpCAM-targeted drugs. In this study, we described the synthesis and evaluation of a site-specifically [99mTc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression. Methods: We first prepared the [99mTc]Tc-HYNIC-G4K; then, it was site-specifically connected to EpCAM-targeted nanobody NB4. The in vitro characteristics of [99mTc]Tc-NB4 were investigated in HT-29 (EpCAM positive) and HL-60 (EpCAM negative) cells, while the in vivo studies were performed using small-animal SPECT/CT in the subcutaneous tumor models and the lymph node metastasis model to verify the specific targeting capacity as well as the potential applications of [99mTc]Tc-NB4. Results: [99mTc]Tc-NB4 displayed a high EpCAM specificity both in vitro and in vivo. SPECT/CT imaging revealed that [99mTc]Tc-NB4 was cleared rapidly from the blood and normal organs except for the kidneys, and HT-29 tumors were clearly visualized in contrast with HL-60 tumors. The uptake value of [99mTc]Tc-NB4 in HT-29 tumors was increased continuously from 3.77 ± 0.39%ID/g at 0.5 h to 5.53 ± 0.82%ID/g at 12 h after injection. Moreover, the [99mTc]Tc-NB4 SPECT/CT could clearly image tumor-draining lymph nodes. Conclusion: [99mTc]Tc-NB4 is a broad-spectrum, specific, and sensitive SPECT radiotracer for the noninvasive imaging of EpCAM expression in the epithelium-derived cancer and revealed a great potential for the clinical translation. [ABSTRACT FROM AUTHOR]

Organic phototransistors (OPTs) are playing an indispensable role in organic optoelectronics, which greatly show their promising application in optical communication, video imaging, missile guidance, and night vision. However, because the thermally activated mode dominated for thin‐film devices leads to a sharp drop in mobility at low temperatures, until now, most of the studies about OPTs are performed at room temperature, severely hindering their further potential optoelectronic application over a broad range of temperatures, especially at low temperature environment. In this work, the optoelectronic properties of a small molecule (2,6‐diphenylanthracene, DPA) based OPTs with band‐like transport are studied at low temperatures. The devices exhibit outstanding optoelectronic properties in terms of mobility (2.6 cm2 V−1 s−1), on/off ratio (≈104), detectivity (1013 Jones), and external quantum efficiency (2500%) even at 150 K, which is superior to the performance of devices with thermally activated mode. In addition, the organic photodetector at low temperatures is also fabricated. Our results demonstrate that organic π‐conjugated DPA small‐molecule has great potential in low‐temperature application. [ABSTRACT FROM AUTHOR]

The limited stability, compatibility, and ion transport capacity of SEI remain key challenges in the development of high-energy–density sodium metal batteries. In order to realize the rational design and facile synthesis of SEI, the influencing factors of different challenges were systematically sorted out. By improving SEI chemical/electrochemical stability, mechanical stability, and thermal stability, the voltage window and temperature range of the battery operation can be effectively broadened. Suppressing the volume effect, phase exfoliation, and phase dissolution to enhance SEI compatibility is crucial for extending battery cycle life. The stability of ion transport at the electrode–electrolyte interface is affected by the composition, structure, and homogeneity of the interfacial phase, and fast and uniform interfacial Na+ transport can enable high-rate, high-safety sodium ion battery designs. [Display omitted] • The challenges and design elements of SEI are summarized comprehensively. • The formation mechanism, characteristics, and failure mechanism of SEI are systematically reviewed. • The latest development of SEI regulation strategy is discussed. • The opportunity and research direction of interface design for long lasting sodium metal batteries are prospected. Inhomogeneous and fragile solid electrolyte interphase (SEI) leads to poor battery cycle life and safety hazards, which is a key challenge that limits the practical application of low-cost sodium metal anodes. Although sodium metal batteries based on non-aqueous liquid and solid electrolytes have made great progress in terms of interfacial chemistry and SEI regulation strategies, the relevant evaluation of SEI from the perspective of the electrolyte is not well understood. This paper reviews the formation mechanism, physicochemical properties, and failure mechanism of SEI at the interface between the sodium metal and the liquid/solid electrolyte, focusing on poor stability, compatibility, interfacial ion transport problems, and influencing factors. Recent advances in SEI regulation are summarized in terms of electrolytes, artificial interphases, and electrode engineering to achieve ideal electrochemical reversibility. The effectiveness of the SEI engineering strategies was evaluated based on a comprehensive review of the interfacial stability in different electrolyte systems. Finally, the challenges associated with rational interface design for long-lasting sodium metal batteries are discussed, along with promising avenues for the same. [ABSTRACT FROM AUTHOR]

Keywords: Charge Transport; Crystal Engineering; Light Emission; Molecular Crystals; Organic Semiconductor EN Charge Transport Crystal Engineering Light Emission Molecular Crystals Organic Semiconductor 1 1 1 11/03/22 20221107 NES 221107 B An anthracene-based molecular crystal b with a unique "slipped herringbone" packing motif was developed by crystal engineering through terminal I tert i -butylation. Appropriate exciton-exciton coupling/electron-phonon coupling originating from the unique crystal packing induces a remarkably strong solid-state emission and efficient charge transport, as reported by Wenping Hu et al. in their Research Article (e202206825). Appropriate exciton-exciton coupling/electron-phonon coupling originating from the unique crystal packing induces a remarkably strong solid-state emission and efficient charge transport, as reported by Wenping Hu et al. in their Research Article (e202206825). [Extracted from the article]

Organic semiconductors with combinative high carrier mobility and efficient solid‐state emission are full of challenges but urgently pursued for developing new emerging optoelectronics. Herein, by delicately regulating the crystal packing of an anthracene‐based molecular crystal via terminal tert‐butylation, we developed a superior high mobility emissive molecule, 2,6‐di(6‐tert‐butylnaphthyl)anthracene (TBU‐DNA). The unique “slipped herringbone” packing motif of TBU‐DNA enables its appropriate exciton‐exciton coupling and electron‐phonon coupling, thus resulting in remarkably high solid‐state emission (photoluminescence quantum yield, ΦF≈74.9 %) and efficacious charge transport (carrier mobility, μ=5.0 cm2 V−1 s−1). Furthermore, OLETs based on TBU‐DNA show an external quantum efficiency (EQE) of 1.8 %, which is among the highest EQE values for single component OLETs reported till now. This work presents a crystal engineering strategy via exquisite molecular design to realize high mobility emissive organic semiconductors. [ABSTRACT FROM AUTHOR]