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Background: Limited data are available on applying circulating tumor DNA (ctDNA) in metastatic triple-negative breast cancer (mTNBC) patients. Here, we investigated the value of ctDNA for predicting the prognosis and monitoring the treatment response in mTNBC patients. Methods: We prospectively enrolled 70 Chinese patients with mTNBC who had progressed after ≤2 lines of chemotherapy and collected blood samples to extract ctDNA for 457-gene targeted panel sequencing. Results: Patients with ctDNA+, defined by 12 prognosis-relevant mutated genes, had a shorter progression-free survival (PFS) than ctDNA− patients (5.16 months vs. 9.05 months, p=0.001), and ctDNA+ was independently associated with a shorter PFS (HR, 95% CI: 2.67, 1.2–5.96; p=0.016) by multivariable analyses. Patients with a higher mutant-allele tumor heterogeneity (MATH) score (≥6.316) or a higher ctDNA fraction (ctDNA%≥0.05) had a significantly shorter PFS than patients with a lower MATH score (5.67 months vs.11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months vs. 12.17 months, p

Employees' emotions have an important effect on their job performance, thus leaders can influence subordinates' emotions through emotional contagion and emotional appeal and ultimately affect their job performance. Based on the affective events theory, this study examines the impact of emotional leadership on the subordinates' job performance, the mediating role of subordinates' positive emotions, and the moderating role of susceptibility to positive emotion. Hierarchical regression analysis of 362 valid questionnaires showed that: (1) emotional leadership has a significant positive effect on subordinates' job performance; (2) subordinates' positive emotion partially mediated the relationship between emotional leadership and subordinates' job performance; (3) subordinates' susceptibility to positive emotion positively moderated the relationship between emotional leadership and positive emotions, i.e., the higher the subordinates' susceptibility to positive emotion, the greater the effect of emotional leadership on their positive emotions. This study validates affective events theory, deepens the understanding of the influence mechanism and boundary conditions of emotional leadership on subordinates' job performance, and provides some references for employee performance management.

Objective: Pyroptosis represents an emerging inflammatory form of programmed cell death. Herein, specific functions and clinical implications of pyroptosis-related genes were systematically characterized in breast cancer.Methods: Expression, somatic mutation and copy number variation of 33 pyroptosis-related genes were assessed in breast cancer from TCGA dataset. Their interactions, biological functions and prognostic values were then observed. By stepwise Cox regression analysis, a pyroptosis-related gene signature was generated. The predictive efficacy in survival was examined by survival analyses, ROCs, univariate and multivariate analyses and subgroup analyses. Associations between risk score (RS) and cancer immunity cycle, HLA, immune cell infiltrations, and immune checkpoints were analyzed.Results: Most of pyroptosis-related genes were abnormally expressed in breast cancer. CASP8, NLRC4, NLRP3, NLRP2, PLCG1, NLRP1, NLRP7, SCAF11, GSDMC, and NOD1 occurred somatic mutations as well as most of them had high frequency of CNV. There were closely interactions between them. These genes were distinctly enriched in immune-related processes. A three-gene signature was generated, containing IL-18, GSDMC, and TIRAP. High RS predicted poorer overall survival, progression, and recurrence. After verification, this RS was an independent and sensitive predictive index. This RS was negatively correlated to cancer immunity cycle. Also, low RS was characterized by high HLA, immune cell infiltrations and immune checkpoints. A nomogram including age and RS was generated for accurately predicting 5-, 8-, and 10-year survival probabilities.Conclusion: Pyroptosis-related genes exert key roles in cancer immunity and might be applied as a prognostic factor of breast cancer.

Abstract Individuals’ continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both social competition and hierarchy. However, the molecular regulatory mechanisms underlying the neural ensemble in the mPFC remains unclear. Here, we demonstrate that in excitatory neurons of prelimbic cortex (PL), lncRNA Sera remodels the utilization of Pkm Exon9 and Exon10, resulting in a decrease in the Pkm1/2 ratio in highly competitive mice. By employing a tet-on/off system, we disrupt or rebuild the normal Pkm1/2 ratio by controlling the expression of Pkm2 in PL excitatory neurons. We find that long-term Pkm2 modulation induces timely competition alteration and hysteretic rank change, through phosphorylating the Ser845 site of GluA1. Together, this study uncovers a crucial role of lncRNA Sera/Pkm2 pathway in the transition of social competition to rank by remodeling neural ensemble in mPFC.

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.

Abstract Hard carbon has been widely used in anode of lithium/sodium ion battery, electrode of supercapacitor, and carbon molecular sieve for CO2 capture and hydrogen storage. In this study the lignin derived hard carbon products are investigated, and the conclusions are abstracted as follows. (1) The lignin derived hard carbon products consist of microcrystal units of sp 2 graphene fragments, jointed by sp 3 carbon atoms and forming sp 2–sp 3 hybrid hard carbon family. (2) From the lignin precursors to the sp 2–sp 3 hybrid hard carbon products, most carbon atoms retain their original electron configurations (sp 2 or sp 3) and keep their composition in lignin. (3) The architectures of lignin-derived hard carbon materials are closely dependent on the forms of their lignin precursors, and could be preformed by different pretreatment techniques. (4) The carbonization of lignin precursors follows the mechanism “carbonization in situ and recombination nearby”. (5) Due to the high carbon ratio and abundant active functional groups in lignin, new activation techniques could be developed for control of pore size and pore volume. In general lignin is an excellent raw material for sp 2–sp 3 hybrid hard carbon products, a green and sustainable alternative resource for phenolic resin, and industrial production for lignin derived hard carbon products would be feasible.

Abstract Microcrystal cellulose (MCC) is a green and sustainable resource that widely exists in various lignocellulose species in percentage 10% to 30%. The fine powder of MCC is often discarded in industrial productions that use lignocellulose as feedstock. The crystal structure of two types of MCC (sugarcane pith and bamboo pith) and their derived carbon materials are studied, and the key findings are summarized as follows. (1) In the MCC refined from sugarcane pith, there are large amount of cellulose 2D crystal, which can be converted to valuable 2D graphene crystal. (2) In the MCC refined from bamboo pith there are large amount of cluster microcrystal cellulose, which can be converted to soft and elastic graphene microcrystal (GMC). (3) The 2D cellulose in MCC of sugarcane pith has large surface area and is easily to be degraded to sugars by acid–base hydrolysis reaction, which can be carbonized to Fullerenes-like carbon spheres. (4) The crystal structures of MCC derived carbon materials are strongly impacted by the crystal structures of MCC, and the carbonization reaction of MCC follows “in situ carbonization” and “nearby recombination” mechanism. In general, the results from this study may open a new way for value-added applications of microcrystal cellulose.