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This paper presents novel techniques for improving the performance of a multi-way spectral clustering framework (Govindu in Proceedings of the 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR’05), vol. 1, pp. 1150–1157, 2005 ; Chen and Lerman, 2007 , preprint in the supplementary webpage) for segmenting affine subspaces. Specifically, it suggests an iterative sampling procedure to improve the uniform sampling strategy, an automatic scheme of inferring the tuning parameter from the data, a precise initialization procedure for K -means, as well as a simple strategy for isolating outliers. The resulting algorithm, Spectral Curvature Clustering (SCC), requires only linear storage and takes linear running time in the size of the data. It is supported by theory which both justifies its successful performance and guides our practical choices. We compare it with other existing methods on a few artificial instances of affine subspaces. Application of the algorithm to several real-world problems is also discussed.

Ferroptosis, a novel non-apoptotic form of cell death, can induce tumor cell death and treatment resistance. Lipid metabolism is closely related to ferroptosis; however, the effect of mammary adipocytes on breast cancer ferroptosis remains to be elucidated. Here, we established the co-culture system of adipocyte-breast cancer cells and revealed the protection of triple-negative breast cancer from ferroptosis by adipocytes. Then, we performed the lipidomics analysis comparing lipid metabolites of co-cultured and normal-cultured cells. Mechanistically, oleic acid secreted from adipocytes inhibited lipid peroxidation and ferroptosis of triple-negative breast cancer cells in the presence of ACSL3. Taken together, mammary adipocytes can protect breast cancer cells from ferroptosis through oleic acid in the presence of ACSL3. These findings could provide new ideas and targets for tumor treatment.

Engineering high‐performance and low‐cost bifunctional catalysts for H2 (hydrogen evolution reaction [HER]) and O2 (oxygen evolution reaction [OER]) evolution under industrial electrocatalytic conditions remains challenging. Here, for the first time, we use the stronger electronegativity of a rare‐Earth yttrium ion (Y3+) to induce in situ NiCo‐layered double‐hydroxide nanosheets from NiCo foam (NCF) treated by a dielectric barrier discharge plasma NCF (PNCF), and then obtain nitrogen‐doped YNiCo phosphide (N‐YNiCoP/PNCF) after the phosphating process using radiofrequency plasma in nitrogen. The obtained N‐YNiCoP/PNCF has a large specific surface area, rich heterointerfaces, and an optimized electronic structure, inducing high electrocatalytic activity in HER (331 mV vs. 2000 mA cm−2) and OER (464 mV vs. 2000 mA cm−2) reactions in 1 M KOH electrolyte. X‐ray absorption spectroscopy and density functional theory quantum chemistry calculations reveal that the coordination number of CoNi decreased with the incorporation of Y atoms, which induce much shorter bonds of Ni and Co ions and promote long‐term stability of N‐YNiCoP in HER and OER under the simulated industrial conditions. Meanwhile, the CoN‐YP5 heterointerface formed by plasma N‐doping is the active center for overall water splitting. This work expands the applications of rare‐Earth elements in engineering bifunctional electrocatalysts and provides a new avenue for designing high‐performance transition‐metal‐based catalysts in the renewable energy field. A N‐YNiCoP nanosheet structure is in situ engineered on Ni–Co foam using a dual‐plasma technique and acts as a bifunctional electrocatalyst for water splitting. The formed rich heterointerfaces and N‐doping effectively tune the electronic states of the catalyst, resulting in high hydrogen evolution reaction and oxygen evolution reaction performances in an alkaline medium at an industrial‐scale current density of 2000 mA cm−2.

Background Glioblastoma is one of the malignant tumors of the central nervous system with high lethality, high disability and low survival rate. Effective induction of its death is one of the existing challenges. In recent studies, heat shock protein 27 (HSP27) has been shown to be associated with ferroptosis; therefore, targeting HSP27 may be a potential therapeutic approach for GBM. Methods Immunohistochemistry and western blot analysis were used to detect the expression of HSP27 in GBM tissues. CCK8, plate clone formation assay, EdU proliferation assay for cell proliferation ability, PI, LDH release assay for cell viability. Reactive oxygen, iron levels, and mitochondrial potential for HSP27 silencing were assayed for ferrotosis in vitro. Western blotting and IP were used to verify the relationship between HSP27 and ACSL4. The effect of knockdown of HSP27 on tumor growth capacity was assessed in an intracranial xenograft model. Results HSP27 was significantly highly expressed in GBM. In vitro experiments, knockdown of HSP27 significantly induced ferroptosis in GBM cells. IP and western blot demonstrated a sumo-ization link between HSP27 and ACSL4. In vivo experiments, HSP27 deficiency retarded tumor growth rate by promoting ferroptosis. Conclusions HSP27 deficiency promotes GBM ferroptosis. Targeting HSP27 may serve as a new direction for GBM treatment.

Objectives To define different clinical phenotypes and assess prognostic factors of adult-onset Still’s disease (AOSD). Methods Overall, 492 patients with AOSD seen between 2004 and 2018 at a single centre were retrospectively studied. Results Of these patients, 78% were female, and the median age at onset was 34 (25–49) years [median (25th–75th percentile)]. The median follow-up time was 7 (3–10) years [median (25th–75th percentile)]. Clinical manifestations at admission were used to subdivide patients with AOSD as follows: systemic inflammation (cluster 1), pure (cluster 2), and intermediate (cluster 3). Each subtype had distinct clinical manifestations and prognoses: cluster 1 (34.6%)—multiple organ manifestations, highest infection rate and mortality, and more than half of the patients with at least one relapse during follow-up; cluster 2 (21.3%)—exclusively female, rash and joint involvement, no internal organ involvement, no mortality, and most of the patients with a monocyclic course; and cluster 3 (44.1%)—less infection rate, no serious complications, and lower mortality rate. The 5- and 10-year survival rates after diagnosis were 92.4% and 86.9%, respectively. Independent risk factors for mortality were age at onset ≥50 (hazard ratio (HR): 6.78, 95% CI: 2.10–21.89), hepatomegaly (HR: 5.05, 95% CI: 1.44–17.70), infection (HR: 15.56, 95% CI: 5.88–41.20), and MAS (HR: 26.82, 95% CI: 7.52–95.60). Conclusion Three subtypes of AOSD were identified with distinct clinical manifestations and prognoses. Age at onset ≥50, hepatomegaly, infection, and MAS were prognostic factors for AOSD mortality.

Background. Rhizomes from Dioscorea collettii are extensively used in traditional medicine for the treatment of arthritic diseases, particularly gouty arthritis (GA). This study aims to investigate whether the total saponin of Dioscorea collettii (TSD) can attenuate monosodium urate (MSU) crystal-induced inflammatory effects by suppressing the activation of the TLR4/NF-κB signaling pathway in vivo and in vitro. Methods. Seventy-two male Wistar rats and THP-1 cells were used in this study. Pathological examination was used to examine the ankle joints of rats. The expression levels of TLR4, NF-κB, MyD88, and IL-1β were detected by qRT-PCR, Western blotting, or immunofluorescence. Results. Compared with those in the normal group, the ankle joints of rats in the model group exhibited significant swelling, synovial tissue hyperplasia, inflammatory cell infiltration, and increased expression of IL-1β protein. The joint swelling degree of rats in the TSD high- and medium-dose groups and the colchicine group was significantly decreased, and the histopathology was obviously improved. TSD and colchicine reduced the levels of IL-1β and TNF-α in synovial fluid. They also decreased the mRNA expression of TLR4, NF-κB, and IL-1β in rat joint synovial tissue and the protein expression of TLR4, MyD88, and NF-κB. NF-κB protein expression in both the cytoplasm and nuclei of THP-1 cells showed the opposite trend. Furthermore, immunofluorescence showed that TSD reduced the nuclear translocation of NF-κBp65 in the model group. Conclusion. TSD exhibits an anti-inflammatory effect in the MSU-induced inflammation model, and the mechanism may be to reduce the production of cytokines by inhibiting the activation of the TLR4/NF-κB signaling pathway.

Hydrogen generated by water electrolysis is considered as one of the most promising protocols to partly replace the roles of traditional fossil fuels. However, high‐performance electrocatalyst satisfied with the industrial requirement still faces significant challenges. Low‐temperature plasma contains numerous high‐energy ions, electrons and other reactive species, which can provide a highly reactive environment for tuning the physio‐chemical structures of catalysts through plasma milling, etching, doping and/or deposition. It is well‐known that high‐temperature micro‐filaments contained in plasmas can cause some special modifications of the catalyst surface, thus effectively adjusting the physio‐chemical structure of latterly engineered compounds. Therefore, low‐temperature plasma technologies, especially the dielectric barrier discharge (DBD) and radio frequency (RF) plasmas, can be considered as a green and sustainable strategy for engineering high‐performance electrocatalysts for water splitting (hydrogen evolution reaction [HER]; oxygen evolution reaction [OER]). Herein, recent progress of DBD and RF plasmas for fabricating and modifying transition metal‐based electrocatalysts (e.g. sulphide, phosphide, selenide, oxide, hydroxide) for hydrogen evolution reaction or OER is comprehensively reviewed, and the role of plasma is also discussed.

Glioma stem cells (GSCs) are the important cause of tumorigenesis, recurrence, and chemo(radio)resistance in glioma. Targeting GSCs helps improve the outcomes of glioma treatment. Polo-like kinase 1 (PLK1) is a member of the serine/threonine protein kinase family, which is highly conserved. In recent years, it has been suggested that increased levels of PLK1 and its activity are associated with tumor progression and poor prognosis. We aimed to identify whether PLK1 plays a critical role in stemness maintenance and apoptosis regulation in GSCs. Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1. Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs. We confirmed that YBX1 knockdown resulted in the apoptosis and DNA damage of GSCs. These findings uncover that PLK1 inhibition induces cell apoptosis and DNA damage in GSCs through YBX1 phosphorylation, providing new insights into the mechanism by which PLK1 inhibition contributes to the apoptosis of and DNA damage in gliomas.

Background Oncolytic virus therapy represents a promising approach in cancer treatment due to its dual mechanisms of direct tumor lysis and immunomodulation. This study aims to evaluate the safety and efficacy of T3011, a novel oncolytic virus, administered intratumorally in patients with advanced solid tumors including head and neck squamous cell carcinoma (HNSCC). Methods This study comprised three parts: Part I (single-dose escalation, 2.5 × 10 5 to 1 × 10 8 PFU/mL), Part II (multiple-dose escalation, 2.5 × 10 7 to 1 × 10 8 PFU/mL), and Part III (expansion phase at the recommended phase 2 dose (RP2D) of 1 × 10 8 PFU/mL). The primary endpoints for Parts I and II were safety and tolerability, with secondary endpoints including viral biodistribution, shedding, pharmacodynamics, and immunogenicity. In Part III, the primary endpoint was preliminary efficacy assessed according to RECIST v1.1 criteria, with safety as a key secondary endpoint. Exploratory endpoints for Parts II and III included pharmacodynamics and immune-related responses assessed by iRECIST criteria. Results Among the 87 patients treated with T3011 monotherapy in Part III, 74 were evaluable for efficacy. This group achieved an objective response rate (ORR) of 6.8% and a disease control rate (DCR) of 39.2%, with a median duration of response (DOR) of 10.6 months. Within the HNSCC cohort ( n  = 28), 24 patients were evaluable, showing an ORR of 12.5% and a DCR of 33.3%. Notable immune modulation was observed with increased CD8 + T-cell infiltration and conversion of PD-L1-negative to PD-L1-positive tumor posttreatment. No dose-limiting toxicities (DLTs) or severe treatment-related adverse events (TRAEs) were reported. Conclusions T3011 shows a favorable safety profile, immune-modulating effects, and preliminary efficacy in patients with advanced solid tumors. Trial registration This study is registered with the China Drug Trial Registry (CTR20192464) and ClinicalTrials.gov (NCT05602792).

Background Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM. Methods Immunohistochemistry and western blotting were used to detect the expression of USP7 in GBM tissues. In vitro apoptosis assay of USP7 inhibition was performed by western blotting, immunofluorescence, and flow cytometry. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Western blotting and IP were used to verify the relationship between USP7 and its substrate. In an in vivo experiment using an intracranial xenograft model in nude mice was constructed to assess the therapeutic effect of target USP7. Results Immunohistochemistry and western blotting confirmed that USP7 was significantly upregulated in glioblastoma samples. In in vitro experiments, inhibition of USP7 in GBM induced significant apoptosis. Co-IP and TMT proteomics identified a key anti-apoptotic substrate of USP7, ADP-ribosylation factor 4 (ARF4). Western blotting and IP confirmed that USP7 interacted directly with ARF4 and catalyzed the removal of the K48-linked polyubiquitinated chain that binded to ARF4. In addition, in vivo experiments revealed that USP7 inhibition significantly suppressed tumor growth and promoted the expression of apoptotic genes. Conclusions Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a novel specific inhibitor of USP7 may be an effective approach for the treatment of GBM.