Gender-specific Single Transcript Level Atlas of Vasopressin and its Receptor (AVPR1a) in the Mouse Brain.

Vasopressin (AVP), a nonapeptide synthesized predominantly by magnocellular hypothalamic neurons, is conveyed to the posterior pituitary the pituitary stalk, where AVP is secreted into the circulation. Known to regulate blood pressure and water homeostasis, it also modulates diverse social behaviors, such as pair-bonding, social recognition and cognition in mammals including humans. Importantly, AVP modulates social behaviors in a gender-specific manner, perhaps, due to gender differences in the distribution in the brain of AVP and its main receptor AVPR1a.

Targeted Microwave Ablation for Prostate Cancer Under Magnetic Resonance Imaging-Ultrasound Fusion and Organ-based Tracking: Final Results from the First Phase 2 Trial (TMA-HK).

Targeted microwave ablation (TMA) is a novel focal therapy modality for prostate cancer (PC). TMA-HK is the first phase 2 trial investigating the efficacy and functional outcomes of transperineal TMA (NCT04113811) in 30 men with low- or intermediate-risk PC. TMA was performed transperineally with magnetic resonance imaging (MRI)-ultrasound fusion guidance and organ-based tracking.

Definition, Classification, and Management of Primary Non-Cardiac Causes of Cardiogenic Shock.

Cardiogenic shock is a complex syndrome presenting with a critical state of cardiac output insufficient to support end-organ perfusion requirements. Contemporary cardiogenic shock classification recognizes broad categories of primary cardiac etiologies of cardiogenic shock, such as acute myocardial infarction and heart failure. Primary non-cardiac etiologies of cardiogenic shock, however, are poorly described in literature and have not been captured by any contemporary classification, leading to challenges in diagnosing and managing these cases.

Protective Mechanism of Proanthocyanidins Against Hydrogen Peroxide-Introduced Oxidative Damage in Adult Retinal Pigment Epithelial-19.

Retinal pigment epithelial (RPE) is an oxidation-resistant cell. But if it is subjected to various harmful stimuli for a prolonged period, an excessive amount of oxyradical will be generated to cause retinal dysfunction. We investigated and elucidated the protective mechanism of proanthocyanidins (SBP) against oxidative damage in RPE.

Age-Dependent Pathogenesis of Influenza A Virus H7N9 Mediated Through PB1-F2-Induced Mitochondrial DNA Release and Activation of cGAS-STING-NF-κB Signaling.

Exactly why human infection of avian influenza A virus H7N9 causes more severe disease in the elderly remains elusive. In this study, we found that H7N9 PB1-F2 is a pathogenic factor in 15-18-month-old BALB/C mice (aged mice) but not in 6-8-week-old young adult mice (young mice). Recombinant influenza A virus with H7N9 PB1-F2-knockout was less pathogenic in aged mice as indicated with delayed weight loss.

Conserved moonlighting protein pyruvate dehydrogenase induces robust protection against infection.

Developing an effective () vaccine has been a challenging endeavor, as demonstrated by numerous failed clinical trials over the years. In this study, we formulated a vaccine containing a highly conserved moonlighting protein, the pyruvate dehydrogenase complex E2 subunit (PDHC), and showed that it induced strong protective immunity against epidemiologically relevant staphylococcal strains in various murine disease models. While antibody responses contributed to bacterial control, they were not essential for protective immunity in the bloodstream infection model.

Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia.

Understanding osteokine biology.

Bone is an endocrine organ that participates in whole-body homeostasis. The biology of bone-derived osteokines, however, remains unclear. Liang et al.

Consideration and Application of Lipoprotein(a) in the Risk Assessment of Atherosclerotic Cardiovascular Disease Risk in Adults.

Lipoprotein(a) (Lp[a]) is an low-density lipoprotein (LDL)-like particle in which apolipoprotein (apo) B is covalently bound to a plasminogen-like molecule called apo(a). A High level of Lp(a) has been demonstrated to be an independent, causal, and prevalent risk factor for atherosclerotic cardiovascular disease (ASCVD), as well as aortic valve disease, through mechanisms that promote atherogenesis, inflammation, and thrombosis. With reliable and accessible assays, Lp(a) level has been established to be associated linearly with the risk for ASCVD.

Born with an advantage: early life and maternal effects on fitness in female ground squirrels.

Lifetime fitness and its determinants are an important topic in the study of behavioral ecology and life-history evolution. Early life conditions comprise some of these determinants, warranting further investigation into their impact. In some mammals, babies born lighter tend to have lower life expectancy than those born heavier, and some of these life-history traits are passed on to offspring, with lighter-born females giving birth to lighter offspring.

Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia.

Hypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the gene encoding tissue non-specific alkaline phosphatase. Doctor Rathbun first described the case of a 3-week-old infant who presented with severe osteopenia, rickets, and multiple radiographic fractures, and died shortly after of epileptic seizure and respiratory distress. The term "hypophosphatasia" was coined as the patients' alkaline phosphatase levels were significantly low.

Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways.

Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues.

Anti-skin aging effect of sea buckthorn proanthocyanidins in D-galactose-induced aging mice.

Oxidative stress in skin cells caused by changes in the external environment is one of the principal causes of skin aging. Sea buckthorn proanthocyanidins (SBPs) have good free radical scavenging ability. We established a senescence model by injecting 500 mg/kg D-galactose into the dorsal necks of mice, and then different doses of SBP (25, 50, and 100 mg/kg) were gavaged to explore the effects of SBP on the skin tissues of senescent mice and elucidate the related mechanism of action.

Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists.

Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology.