Background. Oxidative stress and neuronal apoptosis have important roles in the pathogenesis after intracerebral hemorrhage (ICH). Previous studies have reported that low‐density lipoprotein receptor‐related protein 6 (LRP6) exerts neuroprotection in several neurological diseases. Herein, we investigate the role of LRP6 receptor activation with HLY78 to attenuate oxidative stress and neuronal apoptosis after ICH, as well as the underlying mechanism. Methods. A total of 199 CD1 mice were used. ICH was induced via injection of autologous blood into the right basal ganglia. HLY78 was administered via intranasal injection at 1 h after ICH. To explore the underlying mechanism, LRP6 siRNA and selisistat, a Sirt1 selective antagonist, were injected intracerebroventricularly at 48 h before ICH induction. Neurobehavioral tests, Western blot, and immunofluorescence staining were performed. Results. The expression of endogenous p‐LRP6 was gradually increased and expressed on neurons after ICH. HLY78 significantly improved the short‐ and long‐term neurobehavioral deficits after ICH, which was accompanied with decreased oxidative stress and neuronal apoptosis, as well as increased expression of p‐GSK3β, Sirt1, and PGC‐1α, as well as downregulation of Romo‐1 and C‐Caspase‐3. LRP6 knockdown or Sirt1 inhibition abolished these effects of HLY78 after ICH. Conclusion. Our results suggest that administration of HLY78 attenuated oxidative stress, neuronal apoptosis, and neurobehavioral impairments through the LRP6/GSK3β/Sirt1/PGC‐1α signaling pathway after ICH.

Background: Our previous studies demonstrated that CCL17 and its receptor CCR4 play crucial roles in neuroinflammation and microglial activation following intracerebral hemorrhage (ICH). However, the specific mechanisms by which the CCL17/CCR4 axis regulates microglial polarization and hematoma clearance remain unclear. Aims: This study investigates how the CCL17/CCR4 signaling pathway modulates microglial phenotype transition and enhances hematoma resolution after ICH, building upon our earlier findings showing CCR4's involvement in neuroinflammatory responses. Methods: Using CRISPR‐mediated CCR4 disruption and CCR4 overexpression approaches in a mouse ICH model, we examined neurological outcomes, inflammatory responses, and hematoma volumes. We further evaluated the therapeutic potential of recombinant CCL17 administration. The downstream ERK signaling pathway's role in CCL17/CCR4‐mediated microglial function was investigated through pharmacological inhibition. Results: CCR4 knockout exacerbated neurological deficits, increased neuroinflammation, and enlarged hematomas. In contrast, enhancing CCR4 expression or administering recombinant CCL17 improved functional recovery and provided neuroprotection. Mechanistically, CCL17/CCR4 signaling activated the ERK/AP1/SRA pathway, promoting anti‐inflammatory, phagocytic microglial polarization, evidenced by increased CD206 and SRA expression. ERK inhibition reversed these protective effects. Conclusion: Our findings extend previous work by revealing that the CCL17/CCR4 axis enhances hematoma clearance through the ERK/AP1/SRA pathway‐mediated microglial polarization. This mechanism represents a promising therapeutic target for ICH treatment.

Background: Male genitourinary abscess is one of the serious complications of urinary tract infections (UTIs). There were few researches on the clinical and pathogenic characteristics of male genitourinary abscess. Patients and Methods: A retrospective observational study was conducted between January 2004 and April 2019. Male patients with genitourinary abscess originated from urinary tract, including sites of scrotum, testis, epididymis, spermatic cord, and prostate, were enrolled. Clinical and microbial records were collected and analyzed, and antimicrobial susceptibility testings were performed according to CLSI standard. Whole-genome sequencing was applied to detect the β-lactamase genes and virulence genes, as well as to determine the multilocus-sequence typing (MLST) of the collected Klebsiella pneumoniae (K. pneumoniae) isolates. Results: A total of 22 male patients were included. The main clinical symptoms were fever (86.4%), scrotal swelling (68.2%), local skin warmth (59.1%) and ulceration (45.5%). Urinary irritation was often presented in prostate involved abscess. Ultrasound features had a 94.7% positive rate. Surgical treatment, including abscess drainage, was helpful to the prognosis. No matter where the specimens obtained from, including blood, urine or pus, multidrug-resistant K. pneumoniae was the dominant (11 cases, 50.0%) microorganism in positive cultures. Nine of eleven K. pneumoniae isolates had been preserved and recovered. As for MLST typing, all the nine available isolates of K. pneumoniae belonged to the ST11 type and characterized with bla_KPC-2 carbapenemase gene. Virulence genes rmpA2, ybtS, kfuC, wzi, aerobactin genes (iucABCD and iutA) and type 3 fimbriae genes (mrkAD) were identified in all the K. pneumoniae isolates. Conclusion: It seemed that more patients under 35 years old were vulnerable to genitourinary abscess. There was an increasing trend that multidrug-resistant K. pneumoniae isolates with multiple virulence genes were involved in male genitourinary abscess. Prompt and proper antibiotic use, combined with adequate drainage of the abscess, was important to prognosis.

The Vitamin D Receptor (VDR) is an emerging therapeutic target for neurological injuries, yet its role in neuronal ferroptosis and mitochondrial dynamics following intracerebral hemorrhage (ICH) remains undefined. This study aimed to determine if VDR activation protects neurons by regulating mitochondrial fission via the Cyclic Adenosine Monophosphate - Protein Kinase A - Dynamin-related Protein 1 (cAMP-PKA-DRP1) signaling pathway. We utilized a mouse ICH model and a hemin-induced injury model in primary neurons to evaluate the neuroprotective efficacy of the selective VDR agonist, Paricalcitol (PAL). Our results first establish that VDR is a key neuronal target, as its expression is robustly upregulated in perihematomal neurons both in vivo and in vitro. Systemic PAL administration in mice conferred significant neuroprotection, reducing acute neuronal death, suppressing ferroptosis, and preventing excessive mitochondrial fission, which translated into lasting improvements in long-term cognitive function and synaptic integrity. Mechanistically, we demonstrate that PAL's anti-ferroptotic action is a direct neuroprotective effect, independent of microglial hematoma clearance. The core signaling cascade involves VDR-dependent activation of the cAMP-PKA pathway, leading to an increase in the inhibitory phosphorylation of DRP1 at Ser637. The necessity of this pathway was confirmed as the protective effects of PAL were abrogated by VDR knockdown or cAMP inhibition. Critically, its sufficiency was demonstrated as direct activation of the pathway with an agonist mimicked PAL's anti-ferroptotic effects. Collectively, these findings reveal that VDR activation by paricalcitol ameliorates neuronal injury after ICH by directly inhibiting ferroptosis through the cAMP-PKA-DRP1-mediated preservation of mitochondrial integrity, highlighting a potent therapeutic strategy.