Empagliflozin promotes skin flap survival by activating AMPK signaling pathway.

Flaps are widely used in surgical wound repair, yet distal necrosis poses a significant postoperative challenge, stemming from potential factors such as inadequate blood perfusion, inflammation, ischemia/reperfusion (I/R) injury, mitochondrial impairment, and subsequent ferroptosis. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has pharmacological activities that promote angiogenesis, mitophagy, and inhibit inflammation, I/R injury, and ferroptosis. However, it is unclear whether EMPA can enhance flap survival.

Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival.

Brachial plexus root avulsion (BPRA) injury arises from challenging delivery during childbirth, sports-related incidents, or car accidents, leading to extensive loss of motor neurons (MNs) and subsequent paralysis, including both motor and sensory impairment. Surgical nerve re-implantation cannot effectively restore motor function, and the survival of injured MNs is vital for axon regeneration and re-innervating the target muscles. Therefore, identifying novel molecular targets to improve injured MNs survival is of great significance in the treatment of BPRA injuries.

Correlation analysis of positron emission tomography/computed tomography-magnetic resonance imaging of cannabinoid type 1 receptor in the lumbar spine and brain of aged osteoporosis female cynomolgus monkeys.

Background: Although cannabinoid receptor 1 (CB1R) antagonists can inhibit bone loss in osteoporosis mouse models, different strains of mice show different bone mass phenotypes after knock out the gene. The relationship between CB1R and bone metabolism is complex, and its regulatory role in bone metabolism and as a therapeutic target for osteoporosis requires further investigation.

Methods: Based on lumbar spine volumetric bone mineral density (vBMD) data of healthy female cynomolgus monkeys aged 1-25 years, naturally aged postmenopausal female osteoporotic monkeys and normal young monkeys were screened by detecting lumbar vertebrae vBMD and estradiol levels in this study.

Erratum: FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.

[This corrects the article DOI: 10.1016/j.isci.

Recent developments on the application of molecular probes in multiple myeloma: Beyond [F]FDG.

Multiple myeloma (MM) is a neoplastic plasma cell proliferative disorder characterized by various osteolytic bone destruction as a radiological morphological marker. Functional imaging, particularly nuclear medicine imaging, is a promising method to visualize disease processes before the appearance of structural changes by targeting specific biomarkers related to metabolism ability, tumor microenvironment as well as neoplastic receptors. In addition, by targeting particular antigens with therapeutic antibodies, immuno-PET imaging can support the development of personalized theranostics.

Development of immune deficient FAH-knockout miniature pig.

Human hepatocyte transplantation for liver disease treatment have been hampered by the lack of quality human hepatocytes. Pigs with their large body size, longevity and physiological similarities with human are appropriate animal models for the expansion of human hepatocytes. Here we report on the generation of RAG2IL2RγFAH (RGFKO) pigs CRISPR/Cas9 system and somatic cell nuclear transfer.

Phenylacetyl pepstatin inhibitors of aspartyl proteases from Streptomyces varsoviensis.

A new pepstatin with a phenylacetyl group, pepstatin Pa (1), and its methyl ester (2) were isolated from Streptomyces varsoviensis DSM 40346. Their structures were determined by high-resolution mass spectrometry and nuclear magnetic resonance techniques. The absolute configuration was determined using the Marfey's method.

Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo.

Plasmodium falciparum has developed extensive mechanisms to evade host immune clearance. Currently, most of our understanding is based on in vitro studies of individual parasite variant surface antigens and how this relates to the processes in vivo is not well-understood. Here, we have used a humanized mouse model to identify parasite factors important for in vivo growth.

Positron Emission Tomography in the Neuroimaging of Autism Spectrum Disorder: A Review.

Autism spectrum disorder (ASD) is a basket term for neurodevelopmental disorders characterized by marked impairments in social interactions, repetitive and stereotypical behaviors, and restricted interests and activities. Subtypes include (A) disorders with known genetic abnormalities including fragile X syndrome, Rett syndrome, and tuberous sclerosis and (B) idiopathic ASD, conditions with unknown etiologies. Positron emission tomography (PET) is a molecular imaging technology that can be utilized for dynamic and quantitative research, and is a valuable tool for exploring pathophysiological mechanisms, evaluating therapeutic efficacy, and accelerating drug development in ASD.

Current Development and Challenges of Tetravalent Live-Attenuated Dengue Vaccines.

Dengue is the most common arboviral disease caused by one of four distinct but closely related dengue viruses (DENV) and places significant economic and public health burdens in the endemic areas. A dengue vaccine will be important in advancing disease control. However, the effort has been challenged by the requirement to induce effective protection against all four DENV serotypes and the potential adverse effect due to the phenomenon that partial immunity to DENV may worsen the symptoms upon subsequent heterotypic infection.

Cry3Aa*SpyCatcher Fusion Crystals Produced in Bacteria as Scaffolds for Multienzyme Coimmobilization.

The production of Cry3Aa enzyme fusion crystals in provides a direct method to immobilize individual enzymes and thereby improve their stability and recyclability. Nevertheless, many reactions require multiple enzymes to produce a desired product; thus a general strategy was developed to extend our Cry3Aa technology to multienzyme coimmobilization. Here, we report the direct production of particles comprising a modified Cry3Aa (Cry3Aa*) fused to SpyCatcher002 (Cry3Aa*SpyCat2) for coimmobilization of model enzymes MenF, MenD, and MenH associated with the biosynthesis of menaquinone.

Potential Applications and Perspectives of Humanized Mouse Models.

As medical and pharmacological technology advances, new and complex modalities of disease treatment that are more personalized and targeted are being developed. Often these modalities must be validated in the presence of critical components of the human biological system. Given the incongruencies between murine and human biology, as well as the human-tropism of certain drugs and pathogens, the selection of animal models that accurately recapitulate the intricacies of the human biological system becomes more salient for disease modeling and preclinical testing.

bFGF alleviates diabetes-associated endothelial impairment by downregulating inflammation via S-nitrosylation pathway.

Protein S-nitrosylation is a reversible protein modification implicated in both physiological and pathophysiological regulation of protein function. However, the relationship between dysregulated S-nitrosylation homeostasis and diabetic vascular complications remains incompletely understood. Here, we demonstrate that basic fibroblast growth factor (bFGF) is a key regulatory link between S-nitrosylation homeostasis and inflammation, and alleviated endothelial dysfunction and angiogenic defects in diabetes.

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD).

The Development of Three-DNA Methylation Signature as a Novel Prognostic Biomarker in Patients with Colorectal Cancer.

Aims: The prognosis of colorectal cancer (CRC) remains poor. This study aimed to develop and validate DNA methylation-based signature model to predict overall survival of CRC patients.

Methods: The methylation array data of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) database.

Development and Validation of UHPLC-MS/MS Assay for Therapeutic Drug Monitoring of High-dose Methotrexate in Children with Acute Lymphoblastic Leukemia.

Purpose: Precise and timely detection of methotrexate (MTX) concentration played a key role in high-dose MTX individualization therapy in acute lymphoblastic leukemia (ALL) children to avoid serious adverse effects or nonresponse. This report described a sensibility and validation of ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for therapeutic drug monitoring (TDM) of methotrexate concentration in children's plasma.

Methods: One-step protein precipitation of samples was accomplished by adding 200 μL of acetonitrile to 100 μL of plasma sample.

Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses.

Repeated homologous antigen immunization has been hypothesized to hinder antibody diversification, whereas sequential immunization with heterologous immunogens can educate B cell differentiations towards conserved residues thereby facilitating the generation of cross-reactive immunity. In this study, we developed a sequential vaccination strategy that utilized epitope-decreasing antigens to reinforce the cross-reactivity of T and B cell immune responses against all four serotypes dengue virus. The epitope-decreasing immunization was implemented by sequentially inoculating mice with antigens of decreasing domain complexity that first immunized with DENV1 live-attenuated virus, following by the Envelope protein (Env), and then Env domain III (EDIII) subunit protein.

FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.

FGF13 is an intracellular FGF factor. Its role in cardiomyopathies has been rarely investigated. We revealed that endogenous FGF13 is up-regulated in cardiac hypertrophy accompanied by increased nuclear localization.

Synthesis and preliminary studies of C-labeled tetrahydro-1,7-naphthyridine-2-carboxamides for PET imaging of metabotropic glutamate receptor 2.

Selective modulation of metabotropic glutamate receptor 2 (mGlu) represents a novel therapeutic approach for treating brain disorders, including schizophrenia, depression, Parkinson's disease (PD), Alzheimer's disease (AD), drug abuse and addiction. Imaging mGlu using positron emission tomography (PET) would allow for quantification under physiological and pathological conditions and facilitate drug discovery by enabling target engagement studies. In this paper, we aimed to develop a novel specific radioligand derived from negative allosteric modulators (NAMs) for PET imaging of mGlu.

Synthesis and preliminary evaluation of a novel positron emission tomography (PET) ligand for imaging fatty acid amide hydrolase (FAAH).

Fatty acid amide hydrolase (FAAH) exerts its main function in the catabolism of the endogenous chemical messenger anandamide (AEA), thus modulating the endocannabinoid (eCB) pathway. Inhibition of FAAH may serve as an effective strategy to relieve anxiety and possibly other central nervous system (CNS)-related disorders. Positron emission tomography (PET) would facilitate us to better understand the relationship between FAAH in certain disease conditions, and accelerate clinical translation of FAAH inhibitors by providing in vivo quantitative information.