IGFBP3 induces PD-L1 expression to promote glioblastoma immune evasion.

BACKGROUND: Glioblastoma (GBM) characterized by immune escape is the most malignant primary brain tumors, which has strong immunosuppressive effect. Programmed death ligand-1 (PD-L1) is a recognized immunosuppressive member on the surface of tumor cells, and plays a crucial role in immune evasion of tumors. Actually, little is known about the regulation of PD-L1 expression in GBM. Insulin-like growth factor binding protein 3 (IGFBP3) is upregulated in GBM and is related to poor patient prognosis. However, it remains unclear whether IGFBP3 plays a role in the regulation of PD-L1 expression in GBM. METHODS: The role of IGFBP3 in the glioma immune microenvironment was investigated using the CIBERSORT algorithm. The correlation between IGFBP3 and PD-L1 expression was analyzed using TCGA and CGGA databases. QRT-PCR, immunoblotting and RNA-seq were used to examine the regulatory effect of IGFBP3 on PD-L1 expression. Co-culture assay, cell counting kit (CCK-8), qRT-PCR, ELISA and flow cytometry were performed to explore the function of IGFBP3 in inducing immunosuppression. The biological role of IGFBP3 was verified using immunohistochemical, immunofluorescence and mice orthotopic tumor model. RESULTS: In this study, we analyzed immune cells infiltration in gliomas and found that IGFBP3 may be associated with an immunosuppressive microenvironment. Then, by analyzing TCGA and CGGA databases, our results showed that IGFBP3 and PD-L1 expression were positively correlated in GBM patients, but not in LGG patients. In vitro experiments conducted on different GBM cell lines revealed that the overexpression of IGFBP3 led to an increase in PD-L1 expression, which was reversible upon knockdown IGFBP3. Mechanistically, IGFBP3 activated the JAK2/STAT3 signaling pathway, leading to an increase in PD-L1 expression. Additionally, co-culture experiments results showed IGFBP3 overexpression induced upregulation of PD-L1 expression promoted apoptosis in Jurkat cells, and this effect was blocked by IGFBP3 antibody and PDL-1 inhibitors. Importantly, in vivo experiments targeting IGFBP3 suppressed tumor growth and significantly prolonged the survival of mice. CONCLUSIONS: This research demonstrated IGFBP3 is a novel regulator for PD-L1 expression in GBM, and identified a new mechanism by which IGFBP3 regulates immune evasion through PD-L1, suggesting that IGFBP3 may be a potential novel target for GBM therapy.

Assessing shorebird mortalities due to razor clam aquaculture at key migratory stopover sites in southeastern China.

Aquaculture can provide foraging habitat for birds, but it can also result in intentional and accidental mortality. We examined an overlooked conflict between razor clam (Sinonovacula spp.) aquaculture and declining shorebirds in southeastern China's Fujian and Zhejiang provinces. We surveyed 6 out of 11 internationally important stopover sites for these shorebirds and monitored shorebird mortality in 2 sites (Xinghua Bay, Yueqing Bay) with razor clam aquaculture. We visited an additional 32 sites in these 2 provinces to determine if there was netting in other razor clam farms. Approximately 8-9 km2 of intertidal foraging habitat was covered by horizontal nets to prevent birds from feeding on young razor clams at Xinghua Bay and Yueqing Bay. We conservatively estimated that 13,676 (2.5th-97.5th percentile 8,330-21,285) individual shorebirds were entangled in the nets at the 2 monitored sites in April and May 2021, including 2 endangered and 7 near-threatened species. Mortality of 5 species for which we had sufficient data accounted for 0.76% (black-tailed godwit [Limosa limosa]) to 4.27% (terek sandpiper [Xenus cinereus]) of their total flyway populations. This level of mortality could strongly affect their populations. We found netting at 17 additional razor clam farms, indicating a widespread threat to shorebirds. Although razor clams are typically harvested in late March to early April, nets are left on the mudflats throughout the spring and summer, including when the bulk of shorebird migration takes place. Immediately removing these nets after the clam harvest could prevent most of the spring mortality of shorebirds, although this is unlikely to happen without government regulations or economic incentives. To better assess and mitigate the impacts of this conflict, future research should quantify shorebird mortality at other razor clam farms, including during winter, explore less harmful deterrence methods, and assess the socioeconomic factors driving the conflict.

Evaluación de la mortalidad de aves costeras causada por la acuacultura de almejas navaja en sitios importantes de descanso migratorio en el sureste de China Resumen La acuacultura puede proporcionar hábitats de forrajeo para las aves, pero también puede derivar en muertes accidentales o intencionales. Analizamos un conflicto ignorado entre la acuacultura de almeja navaja (Sinonovacula spp.) y la declinación de aves costeras en las provincias de Fujian y Zhejiang del sureste de China. Censamos seis de los once sitios de descanso con importancia internacional para estas aves y monitoreamos su mortalidad en dos sitios en donde se cría la almeja navaja: la bahía de Xinghua y la de Yueqing. Además, visitamos 32 sitios en estas dos provincias para determinar si existían redes en otras granjas de almeja navaja. Unos 8 ­ 9 km2 del hábitat intermareal de forrajeo estaban cubiertos por redes horizontales para evitar que las aves se alimentaran de las almejas juveniles en ambas bahías. Estimamos moderadamente que 13,676 (2.5° ­ 97.5° percentil 8,330 ­ 21,285) individuos de aves costeras se enredaron en las redes en los dos sitios monitoreados durante abril y mayo de 2021, incluyendo a dos especies en peligro y siete casi amenazadas. La mortalidad de las cinco especies para las cuales tuvimos suficientes datos representó del 0.76% (Limosa limosa) al 4.27% (Xenus cinereus) del total de las poblaciones migratorias. Este nivel de mortalidad podría tener un gran efecto sobre las poblaciones de estas especies. Encontramos redes en 17 granjas más, lo que indica una amenaza extendida para las aves costeras. Aunque es típico que se colecte la almeja navaja a finales de marzo y principios de abril, las redes permanecen durante toda la primavera y el verano, incluso cuando ocurre la mayoría de los vuelos migratorios. La eliminación inmediata de estas redes después de la colecta de almejas podría prevenir la mayoría de las muertes primaverales de las aves costeras, aunque no es probable que esto suceda sin regulaciones gubernamentales o incentivos económicos. Para tener mejores evaluaciones y mitigaciones del impacto de este conflicto, una investigación más profunda debería cuantificar la mortalidad de las aves costeras en otras granjas, incluso durante el invierno, explorar métodos de disuasión menos dañinos y evaluar los factores socioeconómicos que causan el conflicto.

Functional analysis of two mitogen-activated protein kinases involved in thermal resistance of the predatory mite Neoseiulus californicus (Acari: Phytoseiidae).

Predatory mites are important biological control agents used against phytophagous mites and small insects. They face various environmental pressures, especially fluctuating climate factors. Neoseiulus californicus, a commercially available phytoseiid mite, is adapted to a wide range of temperature conditions. We investigated the regulatory mechanisms governing the plastic response of N. californicus for coping with environmental temperature variations. The mitogen-activated protein kinase (MAPK) signaling pathway is a highly conserved pathway of cell signal transduction that responds to environmental stress. We isolated two MAPKK genes (NcMAPKK4 and NcMAPKK6) from N. californicus and studied their functions. Developmental stage-specific expression level analysis showed that in adults, particularly females, NcMAPKK4 and NcMAPKK6 levels were higher than in other developmental stages. The expression level analysis at extremely high and low temperature conditions demonstrated that NcMAPKK4 could be induced significantly by adverse thermal stresses, whereas NcMAPKK6 distinctly responded to heat shock, indicating their different roles in thermal stress responses. After silencing of NcMAPKK4, both heat and cold resistance decreased significantly, whereas NcMAPKK6 knockdown had a greater influence on heat resistance. Knockdown of NcMAPKKs also reduced the activities of antioxidant enzymes, suggesting the regulation of NcMAPKKs was closely related to the antioxidant process in oxidative stress caused by external stimuli. These results indicate an important role of NcMAPKKs in the response to thermal stress and provide insight into the MAPK cascade pathway in the environmental adaptation mechanisms of phytoseiid mites.

Robust covalent pyrazine anchors forming highly conductive and polarity-tunable molecular junctions with carbon electrodes.

In molecular electronics, electrode-molecule anchoring strategies play a crucial role in the design of stable and high-performance functional single-molecule devices. Herein, we employ aromatic pyrazine as anchors to connect a central anthracene molecule to carbon electrodes including graphene and armchair single-walled carbon nanotubes (SWCNTs), and theoretically investigate their atomic structures and electronic transport properties. These molecular junctions can be constructed via condensation reactions of the central molecules terminated with ortho-phenylenediamines with ortho-quinone-functionalized nanogaps of graphene and SWCNT electrodes. With two direct C-N covalent bonds connecting the central molecule site-selectively to carbon electrodes in a coplanar way, pyrazine anchors are advantageous for forming stable and structurally well-defined molecular junctions, being expected to reduce the uncertainty about the electrode-molecule linkage motifs. The junction transport is highly efficient due to the coplanar geometry and the ensuing strong π-type molecule-electrode electronic coupling. Furthermore, our calculations show that molecular junctions with pyrazine anchors and carbon electrodes are usually n-type electronic devices; upon hydrogenation of pyridinic nitrogen atoms, the device polarity can be tuned to p-type, indicating that the pyrazine anchors can also serve as a powerful platform for tailoring in situ the polarity of charge carriers in carbon-electrode molecular electronic devices.

Outcomes in kidney transplantation with mycophenolate mofetil-based maintenance immunosuppression in China: a large-sample retrospective analysis of a national database.

There is no large data analysis reporting the outcome of Chinese kidney transplant patients using mycophenolate mofetil (MMF). This study analyzed 6719 patients from the Chinese Scientific Registry of Kidney Transplantation using MMF, which included 1153 from donation after cardiac death (DCD), 1271 from donation after brain and cardiac death (DBCD), and 4295 from living donor (LD). Compared with the transplants from deceased donor (DD), better outcomes including 3-year graft survival probabilities (LD = 95.8% vs. DD = 91.3%), incidence of delayed graft function (DGF, LD = 2.4% vs. DD = 17.7%), infection (LD = 10.7% vs. DD = 20.7%), graft loss (LD = 2.3% vs. DD = 6.3), and death (LD = 1.3% vs. DD = 3.2%) were shown in the LD group, with similar incidences of acute rejection (AR, LD = 3.7% vs. DD = 4.7%), hyperuricemia (LD = 21.7% vs. DD = 22.2%) within postoperative 1 year, and serum creatinine (Scr) >133 µmol/l at 1 year (LD = 18.8% vs. DD = 18.6%). Nonsignificant differences were found between the DCD and DBCD group. The 5-year survival of patient and graft in the LD group were 97.5% and 93.0%. Adjusted Cox model for graft loss showed significant associations with DGF [hazard ratio 3.7 (95% CI: 2.4, 5.8)], AR [2.8 (1.7, 4.6)], Scr >133 µmol/l at 1 year [2.6 (1.5, 4.2)], hyperuricemia [2.3 (1.6, 3.3)], and DD [1.6 (1.1, 2.4)].

Alkyl-Chain-Regulated Charge Transfer in Fluorescent Inorganic CsPbBr3 Perovskite Solar Cells.

Improved charge extraction and wide spectral absorption promote power conversion efficiency of perovskite solar cells (PSCs). The state-of-the-art carbon-based CsPbBr3 PSCs have an inferior power output capacity because of the large optical band gap of the perovskite film and the high energy barrier at perovskite/carbon interface. Herein, we use alkyl-chain regulated quantum dots as hole-conductors to reduce charge recombination. By precisely controlling alkyl-chain length of ligands, a balance between the surface dipole induced charge coulomb repulsive force and quantum tunneling distance is achieved to maximize charge extraction. A fluorescent carbon electrode is used as a cathode to harvest the unabsorbed incident light and to emit fluorescent light at 516 nm for re-absorption by the perovskite film. The optimized PSC free of encapsulation achieves a maximum power conversion efficiency up to 10.85 % with nearly unchanged photovoltaic performances under 80 %RH, 80 °C, or light irradiation in air.

Hole-Boosted Cu(Cr,M)O2 Nanocrystals for All-Inorganic CsPbBr3 Perovskite Solar Cells.

The all-inorganic CsPbBr3 perovskite solar cell (PSC) is a promising solution to balance the high efficiency and poor stability of state-of-the-art organic-inorganic PSCs. Setting inorganic hole-transporting layers at the perovskite/electrode interface decreases charge carrier recombination without sacrificing superiority in air. Now, M-substituted, p-type inorganic Cu(Cr,M)O2 (M=Ba2+ , Ca2+ , or Ni2+ ) nanocrystals with enhanced hole-transporting characteristics by increasing interstitial oxygen effectively extract holes from perovskite. The all-inorganic CsPbBr3 PSC with a device structure of FTO/c-TiO2 /m-TiO2 /CsPbBr3 /Cu(Cr,M)O2 /carbon achieves an efficiency up to 10.18 % and it increases to 10.79 % by doping Sm3+ ions into perovskite halide, which is much higher than 7.39 % for the hole-free device. The unencapsulated Cu(Cr,Ba)O2 -based PSC presents a remarkable stability in air in either 80 % humidity over 60 days or 80 °C conditions over 40 days or light illumination for 7 days.

An ATP-Responsive Codelivery System of Doxorubicin and MiR-34a To Synergistically Inhibit Cell Proliferation and Migration.

Establishing stimulus-responsive nanosystems for the codelivery of anticancer drug and oligonucleotide is a promising strategy in cancer treatment owing to the combination of chemotherapy and gene therapy in a synergistic manner. Herein, an ATP aptamer and its cDNA sequence were first hybridized to produce the duplex, into which chemotherapeutic agent doxorubicin (DOX) interacted through the GC-rich motif of duplex, and PEI25K was then employed as a carrier to condense the DOX-loading duplex and miR-34a to construct the ternary nanocomplex PEI/DOX-Duplex/miR-34a. The nanocomplex exhibited a favorable drug release profile through the response to high concentration of ATP in the cytosol. The ATP-responsive delivery system was demonstrated to possess higher antiproliferative effect (cell viability of <40%) than the single cargo delivery, which could be attributed to the synergistic induction of cell apoptosis and cell cycle arrest from DOX and miR-34a. Furthermore, wound healing and Transwell assay elucidated the higher antimigration effect of ternary nanocomplex than DOX-Duplex or miR-34a delivery. Overall, the combinatorial delivery of DOX and miR-34a through an ATP-responsive manner could trigger the rapid release of cargoes in the cytosol and enhance the inhibition of cell proliferation and migration through the synergistic manner of these two components.

HIV-1 Vif inhibits G to A hypermutations catalyzed by virus-encapsidated APOBEC3G to maintain HIV-1 infectivity.

BACKGROUND: HIV-1 viral infectivity factor (Vif) is an essential accessory protein for HIV-1 replication. The predominant function of Vif is to counteract Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G, A3G), a potent host restriction factor that inhibits HIV-1 replication. Vif mediates the proteasomal degradation of A3G and inhibits A3G translation, thus diminishing the pool of A3G that is available to be packaged into budding virion. Although Vif is robust in degrading A3G, the protection provided against A3G is not absolute. Clinical and laboratory evidence have shown that A3G is not completely excluded from HIV-1 viral particles during HIV-1 replication. It remains unclear why the viral samples are still infectious when A3G has been packaged into the virions. RESULTS: In this study, we provide evidence that Vif continues to protect HIV-1 from the deleterious effects of A3G, even after packaging of A3G has occurred. When equal amounts of A3G were packaged into budding virions, the virus expressing functional Vif was more infectious and incurred fewer G to A hypermutations in the second round of infection compared to Vif-deficient virus. A Vif mutant with a defect in viral packaging showed a reduced ability to protect the HIV-1 genome from G to A hypermutations. CONCLUSION: Our data suggest that even packaged A3G is still under the tyranny of Vif. Our work brings to light an additional caveat for any therapy that hopes to exploit the Vif-A3G axis. The ideal strategy would not only enhance A3G viral packaging, but also reduce HIV-1 Vif viral encapsidation.

Elevated FAPI Activity in an Adult Brodie Abscess.

ABSTRACT: We report an adult Brodie abscess with elevated activity of 18 F-FDG and 68 Ga-FAPI (fibroblast activating protein inhibitor), mimicking bone metastasis. Our case illustrates that Brodie abscess should also be contemplated in the differential diagnosis of osteolytic lesions with increased 68 Ga-FAPI uptake.

Elevated 68 Ga-FAPI Activity in Pulmonary Inflammatory Pseudotumor.

ABSTRACT: We present a case of pulmonary inflammatory pseudotumor with elevated 68 Ga-FAPI activity. Our case suggested that pulmonary inflammatory pseudotumor should be considered in the differential diagnosis of cancer-like solitary pulmonary nodules with increased 68 Ga-FAPI uptake.

Favorable Response of 225 Ac-PSMA in the Treatment of Castration-Resistant Prostate Cancer With High Bone Metastasis Burden.

ABSTRACT: 225 Ac-PSMA treatment demonstrated low hematologic toxicity for prostate cancer with diffuse red marrow infiltration. A 70-year-old man with diffuse bone metastases of castration-resistant prostate cancer received 225 Ac-PSMA radiation therapy. After 1 treatment cycle, the patient's skeletal lesions demonstrated a significant response and a significant decrease in PSA. 225 Ac-PSMA may be a promising therapeutic option for metastatic castration-resistant prostate cancer patients with high bone metastatic burden.

Significantly Higher 68 Ga-FAPI Than 18 F-FDG Uptake by Hidradenocarcinoma of Head and Neck on PET/CT.

ABSTRACT: Hidradenocarcinoma is quite rare in clinical practice. Herein, we describe the 68 Ga-FAPI and 18 F-FDG PET/CT findings of hidradenocarcinoma of the head and neck in a 75-year-old man. In the present case, the primary tumor and secondary lesions showed intense accumulation of 68 Ga-FAPI but only slight 18 F-FDG uptake. This case demonstrates that 68 Ga-FAPI PET/CT might be used as a helpful tool for evaluating hidradenocarcinoma.

Elevated 68 Ga-FAPI Activity in Klebsiella pneumoniae Invasion Syndrome.

ABSTRACT: Klebsiella pneumoniae invasion syndrome is a rare disease associated with primary liver abscess and secondary extrahepatic infection. We report a case of K. pneumoniae invasion syndrome with elevated 68 Ga-FAPI uptake, mimicking malignancy with multiple metastases. Our case illustrated that K. pneumoniae invasion syndrome should be considered as a possible etiology when diagnosing multiple 68 Ga-FAPI-avid liver foci with metastatic lesions. Besides, PET/CT could be an integrated tool to search for systemic occult lesions in K. pneumoniae invasion syndrome.

Pharmacological inhibition of ICOS attenuates the protective effect of exercise on cardiac fibrosis induced by isoproterenol.

AIMS: To investigate the cardioprotective mechanism of exercise or exercise combined with inducible costimulatory molecules (ICOS) monoclonal antibody (mAb) therapy against isoproterenol (ISO)-induced cardiac remodeling. MAIN METHODS: Totally 24 male C57BL/6J mice were randomly divided into four groups: the control group (normal saline treatment), ISO group (subcutaneous injection of isoproterenol, 10 mg/kg/day, once daily for 5 consecutive days), the exercise with subcutaneous ISO injection group (EPI), and the exercise with injected with ISO and ICOS mAb group (EPII). The mice in EPI and EPII group were trained on a small animal treadmill for 4 weeks (13 m/min, 0% grade, 60min/day). KEY FINDINGS: Exercise significantly attenuated CD45+, Mac-2 inflammatory cell infiltration, cardiac fibrosis and inhibited the RIPK1/RIPK3/MLKL/CaMKII and cardiomyocyte pyroptosis pathways to counter ISO-induced severe cardiac injury. The administration of the ICOS mAb may inhibit the cardioprotection of exercise against ISO-induced heart damage. Compared to those in EPI, our data showed that the increasing levels of myocardial fibrosis, the leukocyte infiltration of cardiac tissue and proteins expression of cardiac myocyte necrosis and pyroptosis signaling pathways in the EPII group. SIGNIFICANCE: Our results demonstrated that exercise decreased leukocyte infiltration in heart, inhibited the cardiomyocyte pyroptosis and necroptosis signaling pathways, and attenuated inflammatory responses to alleviate ISO-induced cardiac fibrosis. However, the antifibrotic effects of combined treatment with exercise and ICOS mAb intervention did not exhibit synergistic enhancement.

The role of vitamin D through SphK1/S1P in the regulation of MS progression.

Sphingosine-1-phosphate (S1P) is biologically active lipid, leading to neuroinflammation and macrophage invasion in central nervous system, plays an important role in the development of multiple sclerosis (MS) model in experimental allergic encephalomyelitis (EAE) rats. Vitamin D is observed to be a key factor in regulating cell S1P levels. We detected vitamin D can alleviate the symptoms of EAE rats, but the exact mechanism is unclear. In PC12 cells, vitamin D can reverse S1P-induced cell death, but the signaling pathway unclear. This study was aimed to investigate S1P regulation mechanism or signaling pathway mediated by vitamin D in EAE and PC12 model. In our experiments, S1P and Sphingosine kinase type 1 (SphK1) mRNA and protein expression in EAE rats group, control group, vitamin D feeding group were detected by HPLC, ELISA, RT-PCR and western blot. PC12 cell death was detected by Propidium (PI) staining. VDR plasmid overexpression and RNA interference, immunofluorescence, real-time cell analysis, protein immunoblotting was used to detect SphK1 transcriptional regulation, cell-substrate attachment quality, the signaling pathway of cell apoptosis and inflammation related gene expression (Bax/Bcl-2, Casepase-3, Il-6, TGF-ß, TNF-α). Our study showed vitamin D can reverse the elevation of S1P level in EAE rats, reduce the severity and shorten the course of EAE. 1,25-(OH) 2D3 coupled with vitamin D receptor (VDR) inhibited SphK1 transcription. 1,25-(OH)2D3 significantly reduced PC12 cell death rate induced by S1P, in addition improved the cell substrate attachment quality. 1,25-(OH) 2D3 can block S1P-induced p-ERK activation and PI3K /Akt signaling pathway reduced Il-6, TGF-ß, TNF-α cytokine release and Bax/Bcl-2, Casepase-3 apoptosis protein expression. On the other hand, immunofluorescence staining showed 1,25-(OH) 2D3 can increase the expression of neuronal perinuclear protein MAP2 in PC12 cells probably protect nerve cells further. In summary, the ameliorative effect of vitamin D was derived from its ability to reduce S1P levels, provides an idea for vitamin D as a combination therapy for disease.

The role of IGFBP-3 in tumor development and progression: enlightenment for diagnosis and treatment.

IGFBP-3 is aberrantly expressed in many tumor types, and its serum and tumor tissue levels provide auxiliary information for assessing the degree of tumor malignancy and patient prognosis, making it a potential therapeutic target for human malignancies and conferring it remarkable clinical value for determining patient prognosis. In this review, we provide a comprehensive overview of the aberrant expression, diverse biological effects, and clinical implications of IGFBP-3 in tumors and its role as a potential prognostic marker and therapeutic target for tumors. In addition, we summarize the signaling pathways through which IGFBP-3 exerts its effects. IGFBP-3 comprises an N-terminal, an intermediate region, and a C-terminal structural domain, each exerting different biological effects in several tumor cell types in an IGF-dependent/non-independent manner. IGFBP-3 shares an intricate relationship with the tumor microenvironment, thereby affecting tumor growth. Overall, IGFBP-3 is an essential regulatory factor that mediates tumor occurrence and progression. Gaining deeper insights into the fundamental characteristics of IGFBP-3 and its role in various tumor types will provide new perspectives and allow for the development of novel strategies for cancer diagnosis, treatment, and prognostic evaluation.

Biodistribution and dosimetry of 177Lu-DOTA-IBA for therapy of bone metastases.

BACKGROUND: We designed and synthesized a novel bisphosphonate radiopharmaceutical (68 Ga- or 177Lu-labeled DOTA-ibandronate [68 Ga/177Lu-DOTA-IBA]) for the targeted diagnosis and treatment of bone metastases. The biodistribution and internal dosimetry of a single therapeutic dose of 177Lu-DOTA-IBA were evaluated using a series of single-photon emission computerized tomography (SPECT) images and blood samples. Five patients with multiple bone metastases were included in this prospective study. After receiving 1110 MBq 177Lu-DOTA-IBA, patients underwent whole-body planar, SPECT/CT imaging and venous blood sampling over 7 days. Dosimetric evaluation was performed for the main organs and tumor lesions. Safety was assessed using blood biomarkers. RESULTS: 177Lu-DOTA-IBA showed fast uptake, high retention in bone lesions, and rapid clearance from the bloodstream in all patients. In this cohort, the average absorbed doses (ADs) in the bone tumor lesions, kidneys, liver, spleen, red marrow, bladder-wall, and osteogenic cells were 5.740, 0.114, 0.095, 0.121, 0.095, and 0.333 Gy/GBq, respectively. Although no patient reached the predetermined dose thresholds, the red marrow will be the dose-limiting organ. There were no adverse reactions recorded after the administration of 1110 MBq 177Lu-DOTA-IBA. CONCLUSION: Dosimetric results show that the ADs for critical organs and total body are within the safety limit and with high bone retention. It is a promising radiopharmaceutical alternative for the targeted treatment of bone metastases, controlling its progression, and improving the survival and quality of life of patients with advanced bone metastasis.

Tuning Surface Organic Structures by Small Gas Molecules through Catassembly and Coassembly.

The field of molecular assembly has seen remarkable advancements across various domains, such as materials science, nanotechnology, and biomedicine. Small gas molecules serve as pivotal modulators, capable of altering the architecture of assemblies via tuning a spectrum of intermolecular forces including hydrogen bonding, dipole-dipole interactions, and metal coordination. Surface techniques, notably scanning tunneling microscopy and atomic force microscopy, have proven instrumental in dissecting the structural metamorphosis and characteristic features of these assemblies at an unparalleled single-molecule resolution. Recent research has spotlighted two innovative approaches for modulating surface molecular assemblies with the aid of small gas molecules: "catassembly" and "coassembly". This Perspective delves into these methodologies through the lens of varying molecular interaction types. The strategies discussed here for regulating molecular assembly structures using small gas molecules can aid in understanding various complex assembly processes and structures and provide guidance for the further fabrication of complex surface structures.

Theranostic in GLP-1R molecular imaging: challenges and emerging opportunities.

Theranostic in nuclear medicine combines diagnostic imaging and internal irradiation therapy using different therapeutic nuclear probes for visual diagnosis and precise treatment. GLP-1R is a popular receptor target in endocrine diseases, non-alcoholic steatohepatitis, tumors, and other areas. Likewise, it has also made breakthroughs in the development of molecular imaging. It was recognized that GLP-1R imaging originated from the study of insulinoma and afterwards was expanded in application including islet transplantation, pancreatic ß-cell mass measurement, and ATP-dependent potassium channel-related endocrine diseases. Fortunately, GLP-1R molecular imaging has been involved in ischemic cardiomyocytes and neurodegenerative diseases. These signs illustrate the power of GLP-1R molecular imaging in the development of medicine. However, it is still limited to imaging diagnosis research in the current molecular imaging environment. The lack of molecular-targeted therapeutics related report hinders its radiology theranostic. In this article, the current research status, challenges, and emerging opportunities for GLP-1R molecular imaging are discussed in order to open a new path for theranostics and to promote the evolution of molecular medicine.