Consolation behavior is defined as an increase in affiliative contact toward a distressed individual and is associated with the physical and emotional well-being of social species. Allogrooming a distressed individual represents a primary form of consolation behavior and is considered as a complex type of empathy. However, the neural mechanisms underlying allogrooming remain poorly understood. In this study, using adult male and female monogamous mandarin voles (Lasiopodomys mandarinus, approximately three-month-old), we demonstrate that individuals exhibited significantly more allogrooming toward a defeated same-sex littermate than toward a defeated stranger, indicating effects of familiarity on consolation. Social interaction with a defeated cagemate elicited more activity of paraventricular nucleus of the hypothalamus (PVN) neurons, medial amygdala (MeA) and PVN oxytocin (OT) neurons compared to interaction with a stranger male. Using cholera toxin subunit B (CTB) as a retrograde tracer, we confirmed that PVN OT neurons project to the MeA. Fiber photometry recording revealed that the activity of both PVN OT neurons projecting to MeA and OTR-expressing neurons in the MeA was significantly elevated during allogrooming a defeated cagemate. Furthermore, in both male and female voles, overexpression of oxytocin receptor (OTR) mRNA in the MeA increased allogrooming time toward a defeated stranger, whereas interference of OTR mRNA expression in the MeA significantly reduced allogrooming toward a defeated cagemate. These findings demonstrate that mandarin voles display different levels of allogrooming toward distressed siblings or strangers and reveal a critical role for the PVN-to-MeA oxytocinergic pathway in encoding and modulating allogrooming behavior.
Background: Obesity represents a global public health burden with continuously increasing prevalence over recent decades. Combination regimens pairing semaglutide (Sema) with additional therapeutic agents have emerged as a major focus for anti-obesity research. Methods: In diet-induced obese (DIO) mice, we evaluated whether oxytocin (Oxt, 3 and 5 mg·kg-1), long-acting oxytocin (la‑Oxt), caffeine, or butyrate could potentiate the anti-obesity efficacy of Sema. We further compared hypothalamic neuronal activity and plasma metabolomic profiles following Sema treatment against dietary restriction (DR), an established intervention for weight loss and metabolic improvement. Results: Whereas Oxt, la‑Oxt, and caffeine did not augment Sema-mediated body weight reduction, butyrate produced significant potentiation of Sema’s anti-obesity effects. Either Sema monotherapy or Sema-butyrate co-administration elevated the number of c-Fos-positive cells in the paraventricular nucleus (PVN) of the hypothalamus. By contrast, DR decreased PVN c-Fos-positive cell number. Butyrate amplified Sema-elicited activation of PVN neuronal activity. Plasma metabolomics revealed limited overlap between the pharmacological interventions and DR, demonstrating orthogonal metabolic responses. Conclusions: These findings identify the Sema-butyrate combination as a promising anti-obesity strategy, and demonstrate that Sema and DR exert divergent effects on both hypothalamic neuronal activity and plasma metabolite levels.
Introduction: Central precocious puberty (CPP) is a prevalent pediatric endocrine disorder resulting from the premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. PLCB1 acts downstream of the KISS1/GPR54 signaling pathway to mediate gonadotropin-releasing hormone (GnRH) secretion, a key event in pubertal initiation. Moreover, VDR is widely expressed in breast tissue, modulates glandular development, and low serum vitamin D levels have been associated with an elevated risk of CPP. This research aimed to investigate the association between genetic variants in the PLCB1 and VDR genes and CPP susceptibility in Hubei Han Chinese girls. Methods: A total of 384 CPP girls and 422 healthy girls from Hubei province were enrolled in this case-control study, which targeted three PLCB1 gene variants (rs932491, rs2235613, rs708910) and three VDR gene variants (rs731236, rs7975232, rs1544410). A comprehensive meta-analysis integrating this study and existing literature was subsequently conducted. Results: For the rs708910, the A allele and AA genotype were identified as protective factors against CPP risk. For the rs7975232, the C allele and CC genotype were significantly associated with a reduced risk of CPP. The subsequent meta-analysis confirmed that both rs708910 and rs7975232 were robustly linked to CPP susceptibility in the Chinese population. Conclusion: The PLCB1 gene rs708910 and VDR gene rs7975232 may represent potential risk-associated variants for CPP in Han Chinese girls. These findings warrant validation in future large-scale, multi-ethnic cohort studies.
Introduction: Somatostatin receptor 2 (SSTR2) has important diagnostic and therapeutic implications in neuroendocrine tumors, but studies on its expression and clinical significance in medullary thyroid carcinoma (MTC) remain limited with inconsistent findings. Methods: SSTR2 expression was evaluated in 75 MTC patients using two scoring methods: the percentage of positive tumor cells and the H-score. Its associations with clinicopathological features were then analyzed. These results were derived from both manual assessment by pathologists and validated using an automated digital analysis platform. Results: Of 75 cases, 61.3% (46) were SSTR2-positive (>5% positive cells), with a median manual H-score of 0.15 (range 0–2.7). A higher manual H-score was associated with octreotide scintigraphy positivity (P = 0.019). Within SSTR2-positive cases, lymph node metastasis decreased from low to high expression (80.0% vs. 73.3% vs. 27.3%, P = 0.015), and the median manual H-score was lower in high-grade than in low-grade tumors (0.00 vs. 0.25, P = 0.010). In univariate analysis, patients with non-high SSTR2 expression (≤50% positive cells) had higher odds of elevated calcitonin at final follow-up (OR 4.17, P = 0.047). Digital and manual assessments showed directionally consistent clinicopathological associations, and the digital H-score correlated strongly with the manual H-score (Spearman ρ = 0.778, P < 0.001). Conclusion: SSTR2 expression in MTC varies widely between patients. High SSTR2 expression appears associated with reduced tumor aggressiveness and a higher likelihood of biochemical cure.
