Gper1 inhibition exacerbates traumatic brain injury-induced neurological impairments in mice.

Background: G protein-coupled estrogen receptor 1 (Gper1) is widely expressed in the brain, while its function in traumatic brain injury (TBI) remains poorly understood. This study aims to investigate the role of Gper1 in TBI pathology and the underlying mechanisms using a mouse model.

Methods: Gper1 knockout (Gper1) mice were generated, and TBI was induced via controlled cortical impact (CCI).

Interferon regulatory factor-1-expressing astrocytes are epigenetically controlled and exacerbate TBI-associated pathology in mice.

Astrocyte heterogeneity is closely associated with the pathophysiology of traumatic brain injury (TBI), particularly in the development of cerebral edema, which is a major contributor to morbidity and mortality in patients with TBI. However, little is known about how certain astrocyte subpopulations contribute to the development of cerebral edema after acute brain injury. Using multiomics approaches, we identified a proinflammatory interferon regulatory factor-1-positive (IRF1) astrocyte cluster that correlates with clinical severity and outcomes in patients with TBI.

Unlocking the Potential of Disulfidptosis: Nanotechnology-Driven Strategies for Advanced Cancer Therapy.

Tumor tissues exhibit elevated oxidative stress, with the cystine-glutamate transporter xCT solute carrier family 7 member 11 (xCT/SLC7A11) protecting cancer cells from oxidative damage by facilitating cystine uptake for glutathione synthesis. Disulfidptosis, a newly identified form of programmed cell death (PCD), occurs in cells with high xCT/SLC7A11 expression under glucose-deprived conditions. Distinct from other PCD pathways, disulfidptosis is characterized by aberrant disulfide bond formation and cellular dysfunction, ultimately resulting in cancer cell death.

Molecular Imaging of B7-H3-Targeting Bispecific T Cell-Engaging Antibody MGD009 in Glioblastoma Models.

Adults diagnosed with glioblastoma (GBM) face an extremely poor prognosis; it is the most aggressive and fatal form of a primary brain tumor. The development of CD3-targeting bispecific antibodies (CD3-bsAbs) has recently gained attention as a promising therapeutic approach for GBM. MGD009, a CD3-bsAb, promotes T-cell-mediated cancer cell death by linking B7-H3 on tumor cells with CD3ε on T cells.

Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the stability, pharmacokinetics, and pharmacodynamics of Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, Lu-LNC1010, for PRRT.

Dansylated Amino Acid-Modified Long-Acting PSMA Derivatives Ga/Lu-LNC1011 as Prostate Cancer Theranostics.

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy has demonstrated promising potential for treating metastatic castration-resistant prostate cancer. Recently, albumin-binding motif-modified PSMA radioligands with prolonged blood circulation were developed to improve tumor uptake and therapeutic effectiveness, properties which, however, were associated with an increased risk of bone marrow toxicity. This study presents new PSMA-targeted radioligands incorporating dansylated amino acids as relatively weak and preferable albumin binders to achieve a fine balance between increased tumor accumulation, safety, and diagnostic efficacy, facilitating a unified approach to theranostics within a single molecular framework.

Prognostic Significance of Preoperative Perihematomal Edema in Spontaneous Cerebellar Hemorrhage After Minimally Invasive Surgery.

Background: Minimally invasive surgery (MIS), including endoscopic evacuation and minimally invasive catheter (MIC) evacuation, has been widely used in patients with spontaneous cerebellar hemorrhage (SCH). However, the long-term prognosis varies widely. Herein, a case-control study nested within a multicenter cohort was conducted to explore the risk factors for unfavorable prognosis in patients with SCH after MIS.

Development of [Ac]Ac‑LNC1011 for targeted alpha-radionuclide therapy of prostate cancer.

Purpose: Prostate-specific membrane antigen (PSMA) radioligand therapy (PRLT) has become a promising option for treating metastatic castration-resistant prostate cancer (mCRPC). Radioligands labelled with the Ga/Lu theranostic pair have been most widely used in the clinic for diagnosis and therapy, respectively. This study aims to develop a novel PSMA-targeted radioligand, LNC1011, radiolabeled with alpha-emitter Ac, to optimise pharmacokinetic properties and assess its potential for targeted alpha therapy (TAT) in prostate cancer treatment.

Surgical results, technical notes and complications of jugular foramen lesions via retroauricular infratemporal fossa approach.

Objective: The objective of this study was to evaluate the clinical effect and safety of the postauricular infratemporal fossa approach (ITFA) in resecting jugular foramen lesions.

Methods: All 25 patients undergoing microsurgery via postauricular ITFA from March 2015 to May 2023 in the Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University were included. The clinical and radiological data were retrospectively analyzed.

Radiomolecular Theranostics With Fibroblast-Activation-Protein Inhibitors and Peptides.

The advancement of theranostics, which combines therapeutic and diagnostic capabilities in oncology, has significantly impacted cancer management. This review explores fibroblast activation protein (FAP) expression in the tumor microenvironment (TME) and its association with various malignancies, highlighting its potential as a theranostic marker for PET/CT imaging using FAP-targeted tracers and for FAP-targeted radiopharmaceutical therapy. We examine the development and clinical applications of FAP inhibitors (FAPIs) and peptides, providing insights into their diagnostic accuracy, initial therapeutic efficacy, and clinical impact across diverse cancer types, as well as the synthesis of novel FAP-targeted ligands.

A Nomogram to Predict Intracranial Hypertension in Moderate Traumatic Brain Injury Patients.

Objective: Patients with moderate traumatic brain injury (mTBI) are under the threat of intracranial hypertension (IHT). However, it is unclear which mTBI patient will develop IHT and should receive intracranial pressure (ICP)-lowering treatment or invasive ICP monitoring after admission. The purpose of the present study was to develop and validate a prediction model that estimates the risk of IHT in mTBI patients.

The mA methyltransferase METTL3 drives neuroinflammation and neurotoxicity through stabilizing BATF mRNA in microglia.

Persistent neuroinflammation and progressive neuronal loss are defining features of acute brain injury including traumatic brain injury (TBI) and cerebral stroke. Microglia, the most abundant type of brain-resident immune cells, continuously surveil the environment and play a central role in shaping the inflammatory state of the central nervous system (CNS). In the study, we discovered that the protein expression of METTL3 (a mA methyltransferase) was upregulated in inflammatory microglia independent of increased Mettl3 gene transcription following TBI in both human and mouse subjects.

Clinical translation of a novel FAPI dimer [Ga]Ga-LNC1013.

Unlabelled: Fibroblast activation protein (FAP) has emerged as a highly promising target for cancer diagnostic imaging and targeted radionuclide therapy. To exploit the therapeutic potential of suitably radiolabeled FAP inhibitors (FAPIs), this study presents the design and synthesis of a series of FAPI dimers to increase tumor uptake and retention. Preclinical evaluation and a pilot clinical PET imaging study were conducted to screen the lead compound with the potential for radionuclide therapy.

Homodimeric peptide radiotracer [Ga]Ga-NOTA-(TMVP1) for VEGFR-3 imaging of cervical cancer patients.

Purpose: Vascular endothelial growth factor receptor 3 (VEGFR-3) plays a critical role in tumor lymphangiogenesis and metastasis, holding promise as a promising therapeutic target for solid tumors. TMVP1 (LARGR) is a 5-amino acid peptide previously identified in our laboratory from bacterial peptide display system that specifically targets VEGFR-3. Radiolabeled TMVP1 can be used for non-invasive imaging of VEGFR-3 expressing tumors.

Trans-Defect Underlay Watertight Duraplasty for Traumatic Anterior Skull Base Dural Defect: Technical Report.

Background: Watertight duraplasty is essential for surgical management of traumatic anterior skull base (ASB) dural defect but challenging in the deep and narrow operative corridor. Here, the authors report a trans-defect underlay watertight duraplasty (TDUWD) technique for traumatic ASB dural defect.

Methods: TDUWD was performed by inserting a free pericranium graft under the dural defect.

miR-10a-5p Regulates the Proliferation and Differentiation of Porcine Preadipocytes Targeting the KLF11 Gene.

In the swine industry, meat quality, color, and texture are influenced by the excessive differentiation of fat cells. miRNAs have emerged as integral regulators of adipose development. This study delves into the influence of miR-10a-5b on the proliferation and differentiation of pig preadipocytes.

A comparison of [F]AlF- and Ga-labeled dual targeting heterodimer FAPI-RGD in malignant tumor: preclinical evaluation and pilot clinical PET/CT imaging.

Unlabelled: Due to the heterogeneity of tumors, strategies to improve the effectiveness of dual-targeting tracers in tumor diagnostics have been intensively practiced. In this study, the radiolabeled [F]AlF-NOTA-FAPI-RGD (denoted as [F]AlF-LNC1007), a dual-targeting heterodimer tracer targeting both fibroblast activation protein (FAP) and integrin αβ to enhance specific tumor uptake and retention, was synthesized and evaluated. The tracer was compared with [Ga]Ga-LNC1007 in preclinical and clinical settings.

Peptide receptor radionuclide therapy (PRRT) in metastatic neuroendocrine tumors of unknown primary (CUP-NETs).

Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumors (NETs) has been explored for more than two decades, but there are only limited data on the treatment of NETs of unknown primary site (CUP-NETs). This study aimed to analyze the long-term outcome, efficacy, and safety of PRRT in patients with CUP-NETs. Patients with pathologically confirmed metastatic CUP-NET who received lutetium-177 (Lu) and/or yttrium-90 (Y) labeled somatostatin analogs between March 2001 and March 2019 were retrospectively reviewed; those patients were referred as cCUP-NETs (clinical CUP-NETs).

A Nonviral piggyBac Transposon-Mediated Method to Generate Large-Scale CAR-NK Cells from Human Peripheral Blood Primary NK Cells.

With the inherent antitumor function and unique "off-the-shelf" potential, genetically engineered human natural killer (NK) cells with chimeric antigen receptors (CARs) bear great promise for the treatment of multiple hematological malignancies and solid tumors. Current methods of producing large-scale CAR-NK cells mainly rely on mRNA transfection and viral vector transduction. However, mRNA CAR-NK cells were not stable in CAR expression while viral vector transduction mostly ended up with low efficiency.