In this paper, the new decoupled distributed sliding-mode control (DSMC) is first proposed for second-order consensus in multiagent systems, which finally solves the fundamental unknown problem for sliding-mode control (SMC) design of coupled networked systems. A distributed full-order sliding-mode surface is designed based on the homogeneity with dilation for reaching second-order consensus in multiagent systems, under which the sliding-mode states are decoupled. Then, the SMC is applied to the decoupled sliding-mode states to reach their origin in finite time, which is the sliding-mode surface. The states of agents can first reach the designed sliding-mode surface in finite time and then move to the second-order consensus state along the surface in finite time as well. The DSMC designed in this paper can eliminate the influence of singularity problems and weaken the influence of chattering, which is still very difficult in the SMC systems. In addition, DSMC proposes a general decoupling framework for designing SMC in networked multiagent systems. Simulations are presented to verify the theoretical results in this paper.

ObjectiveHepatocellular carcinoma (HCC) tumour microenvironment (TME) is highly complex with diverse cellular components organising into various functional units, cellular neighbourhoods (CNs). And we wanted to define CN of HCC while preserving the TME architecture, based on which, potential targets for novel immunotherapy could be identified.DesignA highly multiplexed imaging mass cytometry (IMC) panel was designed to simultaneously quantify 36 biomarkers of tissues from 134 patients with HCC and 7 healthy donors to generate 562 highly multiplexed histology images at single-cell resolution. Different function units were defined by topological analysis of TME. CN relevant to the patients’ prognosis was identified as specific target for HCC therapy. Transgenic mouse models were used to validate the novel immunotherapy target for HCC.ResultsThree major types of intratumour areas with distinct distribution patterns of tumorous, stromal and immune cells were identified. 22 cellular metaclusters and 16 CN were defined. CN composed of various types of cells formed regional function units and the regional immunity was regulated reversely by resident Kupffer cells and infiltrating macrophages with protumour and antitumour function, respectively. Depletion of Kupffer cells in mouse liver largely enhances the T cell response, reduces liver tumour growth and sensitises the tumour response to antiprogrammed cell death protein-1 treatment.ConclusionOur findings reveal for the first time the various topological function units of HCC TME, which also presents the largest depository of pathological landscape for HCC. This work highlights the potential of Kupffer cell-specific targeting rather than overall myeloid cell blocking as a novel immunotherapy for HCC treatment.

A H2S triggered and H2S releasing near-infrared fluorescent probe (HL-H2S) was developed. HL-H2S does not interfere with the progression of ferroptosis by consuming H2S, thus enabling high-fidelity in situ imaging of ferroptosis.

Background: To investigate predictors of postoperative acute intracranial hemorrhage (AIH) and recurrence of chronic subdural hematoma (CSDH) after burr hole drainage. Methods: A multicenter retrospective study of patients who underwent burr hole drainage for CSDH between January 2013 and March 2019. Results: A total of 448 CSDH patients were enrolled in the study. CSDH recurrence occurred in 60 patients, with a recurrence rate of 13.4%. The mean time interval between initial burr hole drainage and recurrence was 40.8 ± 28.3 days. Postoperative AIH developed in 23 patients, with an incidence of 5.1%. The mean time interval between initial burr hole drainage and postoperative AIH was 4.7 ± 2.9 days. Bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independent predictors of recurrence in the multiple logistic regression analyses. Preoperative headache was an independent risk factor of postoperative AIH in the multiple logistic regression analyses, however, intraoperative irrigation reduced the incidence of postoperative AIH. Conclusions: This study found that bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independently associated with CSDH recurrence. Clinical presentation of headache was the strongest predictor of postoperative AIH, and intraoperative irrigation decreased the incidence of postoperative AIH.

Background: The therapeutic efficacy of cisplatin-based chemotherapy for non-small cell lung cancer (NSCLC) is limited by drug resistance. In NSCLC, hyperactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) counteracts oxidative stress to promote chemoresistance. Metformin-mediated downregulation of Nrf2 plays a pivotal role in overcoming drug resistance in NSCLC cells. Therefore, a deeper understanding of the molecular mechanisms of combination therapy and the role of Nrf2 in chemotherapeutic response is critical to clinical translation. Methods:The effects of combination therapy with metformin and cisplatin on cell proliferation and apoptosis, intracellular reactive oxygen species (ROS) levels, and xenograft tumor formation were analyzed in NSCLC cells. Co-immunoprecipitation (co-IP) and Phos-tag assays were used to explore the mechanism of metformin-mediated Nrf2 suppression. Immunohistochemical (IHC) staining was performed to detect Nrf2 expression in matched tumor samples before and after neoadjuvant chemotherapy.Results: Metformin was observed to synergistically augment cisplatin-induced cytotoxicity by strongly inhibiting the level of Nrf2, thereby weakening the antioxidant system and detoxification ability of Nrf2 and enhancing ROS-mediated apoptosis in NSCLC. The synergistic antitumor effect of combination therapy is blocked by treatment with the ROS scavenger N-acetyl cysteine (NAC) as well as overexpression of Nrf2 and its downstream antioxidant protein. Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation. Moreover, for the first time, an association of non-decreased Nrf2 expression in patients after neoadjuvant chemotherapy with poor survival and chemoresistance in NSCLC was revealed.Conclusions: Our findings illustrate the mechanism of metformin-mediated Nrf2 degradation through posttranslational modifications (PTMs), which weakens the ROS defense system in NSCLC. Fluctuations in Nrf2 expression have a strong predictive ability for chemotherapeutic response in neoadjuvant NSCLC patients. Targeting of the Nrf2 pathway could be a therapeutic strategy for overcoming chemoresistance, with metformin as the first choice for this strategy.