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Sociality is among the most important motivators of human behaviour. However, the neural mechanisms determining levels of sociality are largely unknown, primarily due to a lack of suitable animal models. Here, we report the presence of a surprising degree of general sociality in Drosophila . A newly-developed paradigm to study social approach behaviour in flies reveal that social cues perceive through both vision and olfaction converged in a central brain region, the γ lobe of the mushroom body, which exhibite activation in response to social experience. The activity of these γ neurons control the motivational drive for social interaction. At the molecular level, the serotonergic system is critical for social affinity. These results demonstrate that Drosophila are highly sociable, providing a suitable model system for elucidating the mechanisms underlying the motivation for sociality. Robust social attraction in fruit flies relies on two prominent senses, vision and olfaction, which converge to central brain neurons. The neurons of the γ lobe of the mushroom bodies integrate sensory information and modulate social affinity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SummaryDysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16− NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16− and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract, with increasing incidence and mortality rates, posing a significant burden on human health. Its progression relies on various mechanisms, among which the tumor microenvironment and tumor-associated macrophages (TAMs) have garnered increasing attention. Macrophage infiltration in various solid tumors is associated with poor prognosis and is linked to chemotherapy resistance in many cancers. These significant biological behaviors depend on the heterogeneity of macrophages. Tumor-promoting TAMs comprise subpopulations characterized by distinct markers and unique transcriptional profiles, rendering them potential targets for anticancer therapies through either depletion or reprogramming from a pro-tumoral to an anti-tumoral state. Single-cell RNA sequencing technology has significantly enhanced our research resolution, breaking the traditional simplistic definitions of macrophage subtypes and deepening our understanding of the diversity within TAMs. However, a unified elucidation of the nomenclature and molecular characteristics associated with this diversity remains lacking. In this review, we assess the application of conventional macrophage polarization subtypes in colorectal malignancies and explore several unique subtypes defined from a single-cell omics perspective in recent years, categorizing them based on their potential functions.

Enhanced aerobic glycolysis constitutes an additional source of energy for tumor proliferation and metastasis. Human papillomavirus (HPV) infection is the main cause of cervical cancer (CC); however, the associated molecular mechanisms remain poorly defined, as does the relationship between CC and aerobic glycolysis. To investigate whether HPV 16/18 E6/E7 can enhance aerobic glycolysis in CC, E6/E7 expression was knocked down in SiHa and HeLa cells using small interfering RNA (siRNA). Then, glucose uptake, lactate production, ATP levels, reactive oxygen species (ROS) content, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were evaluated. RNA-seq was used to probe the molecular mechanism involved in E6/E7-driven aerobic glycolysis, and identified IGF2BP2 as a target of E6/E7. The regulatory effect of IGF2BP2 was confirmed by qRT-PCR, western blot, and RIP assay. The biological roles and mechanisms underlying how HPV E6/E7 and IGF2BP2 promote CC progression were confirmed in vitro and in vivo. Human CC tissue microarrays were used to analyze IGF2BP2 expression in CC. The knockdown of E6/E7 and IGF2BP2 attenuated the aerobic glycolytic capacity and growth of CC cells, while IGF2BP2 overexpression rescued this effect in vitro and in vivo. IGF2BP2 expression was higher in CC tissues than in adjacent tissues and was positively correlated with tumor stage. Mechanistically, E6/E7 proteins promoted aerobic glycolysis, proliferation, and metastasis in CC cells by regulating MYC mRNA m6A modifications through IGF2BP2. We found that E6/E7 promote CC by regulating MYC methylation sites via activating IGF2BP2 and established a link between E6/E7 and the promotion of aerobic glycolysis and CC progression. Blocking the HPV E6/E7-related metabolic pathway represents a potential strategy for the treatment of CC.

Background CAR-T cell therapy represents a major breakthrough in hematological malignancies. However, the trade-off between insufficient treatment persistence and treatment-related toxicities (especially cytokine release syndrome, CRS) still limits its wider clinical application. Main body Our review aims to reframe the understanding of this central dilemma. It posits that the dynamic imbalance of intracellular signaling networks and external inflammation in the tumor microenvironment (TME) are the causes of insufficient persistence of CAR-T cells and the severe CRS. The intracellular signaling network and the influence of the external TME jointly regulate CAR-T cell persistence and inflammatory response. We explore strategies for designing CAR-T cells that simultaneously enhance persistence and mitigate severe CRS risk. The next-generation goal is to achieve an optimal therapeutic outcome in which CAR-T cells exhibit sustained antitumor efficacy alongside a favorable safety profile. Conclusion The central thesis posits that persistence and safety do not have to be chosen one at the expense of the other. Rather, the relationship between persistence and CRS exists in harmony. Through the precise modulation, it is feasible to simultaneously enhance CAR-T cell persistence while effectively mitigating CRS. This review paints a blueprint for the next-generation CAR-T cell therapies that are both more persistent and inherently safer. Graphical Abstract

Objective Postoperative pancreatic fistula (POPF) remains a major postoperative complication of laparoscopic distal pancreatectomy (LDP) that severely impacts surgical safety and patient prognosis. This study was designed to investigate the clinical efficacy of the reinforced U-shaped suture technique in reducing the incidence of POPF after LDP, and to identify independent risk factors for POPF to provide evidence-based references for clinical practice. Methods Data were collected from 165 patients who underwent LDP between 2018 and February 2025 in our institution. Patients were stratified into two groups based on the reinforcement technique employed for pancreatic stump closure: Group A: non-reinforced U-shaped suture with 113 patients; Group B: reinforced U-shaped suture with 52 patients. Propensity score matching (PSM) was used to balance baseline covariates between the two groups. Clinical data of all patients were collected, and univariate and multivariate logistic regression analyses were performed to screen independent risk factors for POPF, and to compare the clinical outcomes of the two groups. Results Using multivariate analysis, pancreatic stump reinforcement technique, including our method, and other well-known POPF risk factors were independently assessed. Multivariate logistic regression analysis identified intraoperative bleeding (≥ 345.00 mL) (OR = 8.08, 95% CI: 2.41–27.11, p  < 0.001) and non reinforced U-shaped suture (Group A, Group B OR = 0.18, 95% CI: 0.05–0.65, p  = 0.009) as independent risk factors for POPF. Additionally, pancreatic duct diameter ≥ 3.00 mm (OR = 0.11, 95% CI: 0.03–0.39, p  < 0.001) and hard pancreatic texture (OR = 0.20, 95% CI: 0.06–0.68, p  = 0.011) were identified as independent protective factors for POPF. Compared with Group A, Group B had a significantly lower incidence of clinically relevant grade B/C POPF, and presented more favorable perioperative outcomes including shorter hospital stay and lower hospitalization costs. Conclusion The reinforced U-shaped suture technique is a feasible and cost-effective pancreatic stump closure method for LDP, which is associated with a lower incidence of clinically relevant grade B/C POPF and more favorable perioperative outcomes. Its proposed dual technical characteristics of staple-line mechanical stabilization and indirect pancreatic duct compression/sealing may contribute to the reduction of POPF risk, and the technique holds particular clinical value for high-risk populations awaiting further prospective validation.

Cervical cancer (CC) is the most common gynecologic malignancy, which seriously threatens the health of women. Lipid metabolism is necessary for tumor proliferation and metastasis. However, the molecular mechanism of the relationship between CC and lipid metabolism remains poorly defined. We revealed the expression of IGF2BP3 in CC exceeded adjacent tissues, and was positively associated with tumor stage using human CC tissue microarrays. The Cell Counting Kit-8, colony formation assay, 5-ethynyl-2′-deoxyuridine assay, transwell assays, wound-healing assays, and flow cytometry assessed the role of IGF2BP3 in proliferation and metastasis of CC cells. Besides, exploring the molecular mechanism participating in IGF2BP3-driven lipid metabolism used RNA-seq, which determined SCD as the target of IGF2BP3. Further, lipid droplets, cellular triglyceride (TG) contents, and fatty acids were accessed to discover that IGF2BP3 can enhance lipid metabolism in CC. Moreover, RIP assay and methylated RNA immunoprecipitation experiments seeked the aimed-gene-binding specificity. Lastly, the IGF2BP3 knockdown restrained CC growth and lipid metabolism, after which SCD overexpression rescued the influence in vitro and in vivo using nude mouse tumor-bearing model. Mechanistically, IGF2BP3 regulated SCD mRNA m6A modifications via IGF2BP3-METTL14 complex, thereby enhanced CC proliferation, metastasis, and lipid metabolism. Our study highlights IGF2BP3 plays a crucial role in CC progression and represents a therapeutic latent strategy. It is a potential tactic that blocks the metabolic pathway relevant to IGF2BP3 with the purpose of treating CC.