The neural mechanisms of identifiable victim effect in prosocial decision-making.

The phenomenon known as the "identifiable victim effect" describes how individuals tend to offer more assistance to victims they can identify with than to those who are vague or abstract. The neural underpinnings of this effect, however, remain elusive. Our study utilized functional magnetic resonance imaging to delve into how the "identifiable victim effect" influences prosocial decision-making, considering different types of helping costs, across two distinct tasks. Participants were instructed to decide whether to help a victim with personal information shown (i.e., the identifiable victim) and an unidentifiable one by costing their money (task 1) or physical effort (task 2). Behaviorally, we observed a pronounced preference in both tasks for aiding identifiable victims over anonymous ones, highlighting a robust "identifiable victim effect." On a neural level, this effect was associated with heightened activity in brain areas like the bilateral temporoparietal junction (TPJ) when participants confronted anonymous victims, potentially indicating a more intensive mentalizing process for less concrete victims. Additionally, we noted that the TPJ's influence on value judgment processes is mediated through its functional connectivity with the medial prefrontal cortex. These insights contribute significantly to our understanding of the psychological and neural dynamics underlying the identifiable victim effect.

Immune landscape and heterogeneity of cervical squamous cell carcinoma and adenocarcinoma.

Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients' prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.

Single-nucleus RNA sequencing reveals heterogenous microenvironments and specific drug response between cervical squamous cell carcinoma and adenocarcinoma.

BACKGROUND: Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity of tumor and immune microenvironment remains elusive. METHODS: Here, we performed single-nucleus RNA sequencing (snRNA-seq) from five CSCC and three CAde samples, and systematically outlined their specific transcriptome atlas. FINDINGS: We found CD8+ T cells in CSCC were more cytotoxic but lower exhausted compared to those in CAde, and phagocytic MRC1+ macrophages were specifically enriched in CSCC. Interestingly, we discovered that pro-tumoral cancer-associated myofibroblasts (myoCAFs) and cancer-associated vascular-fibroblasts (vCAFs) were more abundant in CSCC, and further verified their pro-metastatic roles in vitro. Furthermore, we also identified some specific chemotherapy drugs for CSCC (Dasatinib and Doramapimod) and CAde (Pyrimethamine and Lapatinib) by revealing their heterogeneity in transcriptomic profiles of malignant epithelial cells, and further verified their specific sensitivity in cell lines and constructed CC-derived organoids. Cell-cell communication networks revealed that the pathways of NRG1-ERBB2, and FN1-ITAG3 were specific for CAde and CSCC, respectively, which may partly explain the specificities of identified chemotherapy drugs. INTERPRETATION: Our study described the immune heterogeneity and specific cellular interactions between CSCC and CAde, which could provide insights for uncovering pathogenesis and designing personalized treatment. FUNDINGS: National Key R&D Program of China (2021YFC2701201), National Natural Science Foundation of China (82072895, 82141106, 82103134, 81903114).

Prosocial decision-making under time pressure: Behavioral and neural mechanisms.

The present study employed a novel paradigm and functional magnetic resonance imaging (fMRI) to uncover the specific regulatory mechanism of time pressure and empathy trait in prosocial decision-making, compared to self-decision making. Participants were instructed to decide whether to spend their own monetary interest to alleviate themselves (or another person) from unpleasant noise threats under high and low time pressures. On the behavioral level, results showed that high time pressure had a significant effect on reducing participants' willingness to spend money on relieving themselves from the noise, while there is a similar but not significant trend in prosocial decision-making. On the neural level, for self-concerned decision-making, low time pressure activated the bilateral insula more strongly than high time pressure. For prosocial decision-making, high time pressure suppressed activations in multiple brain regions related to empathy (temporal pole, middle temporal gyrus, and inferior frontal gyrus), valuation (medial orbitofrontal cortex), and emotion (putamen). The functional connectivity strength among these regions, especially the connectivity between the medial orbitofrontal cortex and putamen, significantly predicted the effect of time pressure on prosocial decision-making at the behavioral level. Additionally, we discovered the activation of the medial orbitofrontal cortex partially mediated the effect of empathy trait scores on prosocial decision-making. These findings suggest that (1) there are different neural underpinnings for the modulation of time pressure for self and prosocial decision-making, and (2) the empathy trait plays a crucial role in the latter.

Fibroblast diversity and plasticity in the tumor microenvironment: roles in immunity and relevant therapies.

Cancer-associated fibroblasts (CAFs), enriched in the tumor stroma, have received increasing attention because of their multifaceted effects on tumorigenesis, development, metastasis, and treatment resistance in malignancies. CAFs contributed to suppressive microenvironment via different mechanisms, while CAFs also exerted some antitumor effects. Therefore, CAFs have been considered promising therapeutic targets for their remarkable roles in malignant tumors. However, patients with malignancies failed to benefit from current CAFs-targeted drugs in many clinical trials, which suggests that further in-depth investigation into CAFs is necessary. Here, we summarize and outline the heterogeneity and plasticity of CAFs mainly by exploring their origin and activation, highlighting the regulation of CAFs in the tumor microenvironment during tumor evolution, as well as the critical roles performed by CAFs in tumor immunity. In addition, we summarize the current immunotherapies targeting CAFs, and conclude with a brief overview of some prospects for the future of CAFs research in the end. Video Abstract.

A bottleable super-electron-donor for catalytic borylation of aryl halides.

[(Dpp-bian)B(DMAP)]2 (dpp-bian = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene, DMAP = 4-(dimethylamino)pyridine), a bottleable super electron donor (SED), was demonstrated to serve as a SED catalyst in the borylation of aryl iodides, bromides, and the more challenging chlorides. Apart from installing Bpin from B2pin2, the SED-catalyzed borylation protocol is also applicable for installing Bdan from Bpin-Bdan. The radical mechanism has been confirmed by the radical trapping and radical clock experiments.

The prognosis of patients with small cell carcinoma of the cervix: a retrospective study of the SEER database and a Chinese multicentre registry.

BACKGROUND: Small cell carcinoma of the cervix is a rare but poor prognosis pathological type of cervical cancer, for which advice in clinical guidelines is unspecific. We therefore aimed to investigate the factors and treatment methods that affect the prognosis of patients with small cell carcinoma of the cervix. METHODS: In this retrospective study, we collected data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries cohort and a Chinese multi-institutional registry. The SEER cohort included females diagnosed with small cell carcinoma of the cervix between Jan 1, 2000, and Dec 31, 2018, whereas the Chinese cohort included women diagnosed between Jun 1, 2006, and April 30, 2022. In both cohorts, eligibility was limited to female patients older than 20 years with a confirmed diagnosis of small cell carcinoma of the cervix. Participants who were lost to follow-up or those for whom small cell carcinoma of the cervix was not the primary malignant tumour were excluded from the multi-institutional registry, and those with an unknown surgery status (in addition to those for whom small cell carcinoma of the cervix was not the primary malignant tumour) were excluded from the SEER data. The primary outcome of this study was overall survival (length of time from the date of first diagnosis until the date of death from any cause, or the last follow-up). Kaplan-Meier analysis, propensity score matching, and Cox-regression analyses were used to assess treatment outcomes and risk factors. FINDINGS: 1288 participants were included in the study; 610 in the SEER cohort and 678 in the Chinese cohort. Both univariable and multivariable Cox regression analysis (SEER hazard ratio [HR] 0·65 [95% CI 0·48-0·88], p=0·0058; China HR 0·53 [0·37-0·76], p=0·0005) showed that surgery was associated with a better prognosis. In subgroup analyses, surgery remained a protective factor for patients with locally advanced disease in both cohorts (SEER HR 0·61 [95% CI 0·39-0·94], p=0·024; China HR 0·59 [0·37-0·95]; p=0·029). Furthermore, the protective effect of surgery was observed among patients with locally advanced disease after propensity score matching in the SEER cohort (HR 0·52 [95% CI 0·32-0·84]; p=0·0077). In the China registry, surgery was associated with better outcomes in patients with stage IB3-IIA2 cancer (HR 0·17 [95% CI 0·05-0·50]; p=0·0015). INTERPRETATION: This study provides evidence that surgery improves outcomes of patients with small cell carcinoma of the cervix. Although guidelines recommend non-surgical methods as first-line treatment, patients with locally advanced disease or stage IB3-IIA2 cancer might benefit from surgery. FUNDING: The National Key R&D Program of China and the National Natural Science Foundation of China.

Multi-omics data reveals novel impacts of human papillomavirus integration on the epigenomic and transcriptomic signatures of cervical tumorigenesis.

Integration of human papilloma virus (HPV) DNA into the human genome may progressively contribute to cervical carcinogenesis. To explore how HPV integration affects gene expression by altering DNA methylation during carcinogenesis, we analyzed a multiomics dataset for cervical cancer. We obtained multiomics data by HPV-capture sequencing, RNA sequencing, and Whole Genome Bisulfite Sequencing from 50 patients with cervical cancer. We detected 985 and 485 HPV-integration sites in matched tumor and adjacent paratumor tissues. Of these, LINC00486 (n = 19), LINC02425 (n = 11), LLPH (n = 11), PROS1 (n = 5), KLF5 (n = 4), LINC00392 (n = 3), MIR205HG (n = 3) and NRG1 (n = 3) were identified as high-frequency HPV-integrated genes, including five novel recurrent genes. Patients at clinical stage II had the highest number of HPV integrations. E6 and E7 genes of HPV16 but not HPV18 showed significantly fewer breakpoints than random distribution. HPV integrations occurring in exons were associated with altered gene expression in tumor tissues but not in paratumor tissues. A list of HPV-integrated genes regulated at transcriptomic or epigenetic level was reported. We also carefully checked the candidate genes with regulation pattern correlated in both levels. HPV fragments integrated at MIR205HG mainly came from the L1 gene of HPV16. RNA expression of PROS1 was downregulated when HPV integrated in its upstream region. RNA expression of MIR205HG was elevated when HPV integrated into its enhancer. The promoter methylation levels of PROS1 and MIR205HG were all negatively correlated with their gene expressions. Further experimental validations proved that upregulation of MIR205HG could promote the proliferative and migrative abilities of cervical cancer cells. Our data provides a new atlas for epigenetic and transcriptomic regulations regarding HPV integrations in cervical cancer genome. We demonstrate that HPV integration may affect gene expression by altering methylation levels of MIR205HG and PROS1. Our study provides novel biological and clinical insights into HPV-induced cervical cancer.

A novel cuproptosis-related gene signature for overall survival prediction in uterine corpus endometrial carcinoma (UCEC).

Cuproptosis is a copper-dependent model of cell death involved in tumor genesis and progression. Its roles in uterine corpus endometrial carcinoma (UCEC) remains elusive. Here, we aimed to explore the expression and prognostic values of cuprotosis-related genes (CRGs) in UCEC. Expression profiles and clinical data of UCEC were downloaded from The Cancer Genome Atlas (TCGA), and randomly divided into testing or training cohort (1:1 ratio). The CRG signature was identified by LASSO regression analysis. The differentially expressed genes and their functional enrichment analysis were performed by the "limma" R package and Metascape, respectively. The immunocytes infiltration was measured by TIMER, and "GSVA" R package. In total, seven differentially expressed prognostic genes of CRGs in UCEC were identified, and four genes (GLS, CDKN2A, PC, and SUCLG1) were selected to construct a predictive model in training cohort. UCEC patients from training and testing cohorts were further divided into high- or low-risk groups according to the median risk score. High-risk group favored poor prognosis compared to low-risk group. Functional enrichment analysis revealed this CRG signature were got involved in the process of cell-cell adhesion and immune activities (e.g., IL-1 signaling pathway, cellular response to cytokine stimulus). Further analyses revealed there were significant differences between high- and low-risk patients regarding immunocytes infiltration, chemokines, and chemokine receptors. Finally, the expression and biological functions of identified CRGs were confirmed by UCEC samples and experimental methods in vitro. In summary, the CRG signature was significantly correlated with patients' overall survival, which could provide insights into the diagnosis and prognosis prediction for UCEC.

4D label-free quantitative proteomics analysis to screen potential drug targets of Jiangu Granules treatment for postmenopausal osteoporotic rats.

Background: Postmenopausal osteoporosis (PMOP) is a disease with a high prevalence in postmenopausal women and is characterized by an imbalance in bone metabolism, reduced bone mass, and increased risk of fracture due to estrogen deficiency. Jiangu granules (JG) is a compound prescription used in traditional Chinese medicine to treat PMOP. However, its definitive mechanism in PMOP is unclear. This study used a 4D label-free quantitative proteomics method to explore the potential therapeutic mechanism of JG in an ovariectomy (OVX) rats' model. Materials and methods: A rat model of PMOP was established by removing the ovaries bilaterally. Nine 3-month-old specific-pathogen-free female SD rats. The nine rats were randomly divided into 3 groups (n = 3 in each group): the sham-operated group (J), the ovariectomy group (NC), and the JG treatment (ZY) group. Proteins extracted from the bone tissue of the lumbar spine (L3, L4) of three groups of rats were analyzed by 4D label-free quantitative proteomics, and proteins differentially expressed after JG treatment and proteins differentially expressed after de-ovulation were intersected to identify proteins associated with the mechanism of PMOP by JG treatment. Result: There were 104 up-regulated and 153 down-regulated differentially expressed proteins (DEPs) in the J group vs. NC group, 107 up-regulated and 113 down-regulated DEPs in the J group vs. ZY group, and 15 up-regulated and 32 down-regulated DEPs in the NC group vs. ZY group. Six potential target proteins for JG regulation of osteoblast differentiation in OVX rats were identified by taking intersections of differential proteins in the J group vs. NC group and NC group vs. ZY group. Conclusion: JG may exert therapeutic effects by modulating the expression levels of target proteins associated with osteoblast differentiation to enhance osteoblast differentiation in OVX rats. These results further uncovered the target proteins and specific mechanisms of JG in treating PMOP, providing an experimental basis for the clinical application of JG in treating PMOP.

Highly selective, sensitive and fluorescent sensing of dimeric G-quadruplexes by a dimeric berberine.

This paper describes the highly selective, sensitive and topology-specific fluorescent sensing of dimeric G-quadruplexes by a polyether-tethered dimeric berberine 1. Compound 1 displays high selectivity for dimeric G-quadruplexes over monomeric ones, and can be lit up by dimeric G-quadruplexes, in particular by the one linked with one TTA subunit. In addition, it shows no effect on the topology or thermal stability of the G-quadruplexes.