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Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies are currently used in the clinic to interupt the PD-1/PD-L1 immune checkpoint, which reverses T cell dysfunction/exhaustion and shows success in treating cancer. Here, we report a histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), which inhibits tumour histone demethylase Jumonji domain-containing 1A (JMJD1A) and thus downregulates its downstream β-catenin and subsequent PD-L1, providing an antibody-independent paradigm interrupting the PD-1/PD-L1 checkpoint. Synergistically, IOX1 inhibits cancer cells’ P-glycoproteins (P-gp) through the JMJD1A/β-catenin/P-gp pathway and greatly enhances doxorubicin (DOX)-induced immune-stimulatory immunogenic cell death. As a result, the IOX1 and DOX combination greatly promotes T cell infiltration and activity and significantly reduces tumour immunosuppressive factors. Their liposomal combination reduces the growth of various murine tumours, including subcutaneous, orthotopic, and lung metastasis tumours, and offers a long-term immunological memory function against tumour rechallenging. This work provides a small molecule-based potent cancer chemo-immunotherapy. Some chemotherapeutic drugs, such as doxorubicin, induce immunogenic cell death (ICD) and promote anti-tumor immune responses. Here the authors report that the histone demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX1) reduces the expression of PD-L1 in cancer cells and enhances doxorubicin-induced ICD, promoting T cell infiltration and reducing tumor growth in preclinical models.

This paper conducted an experimental study of droplet behavior characteristics occurring within a burning aviation kerosene droplet and on the droplet interface. The droplet combustion was performed in a quiescent high-temperature environment by means of the droplet suspension technique. The soot particles were used as tracers to visualize the fluid motion in the droplet. The shape variation of droplet, internal flow pattern in the burning droplet, and instabilities at gas-liquid phase interface were recorded by a high speed camera. The internal fluid flow in the droplet was revealed to be caused by the Marangoni effect, which was generated because of the surface tension gradient induced by the temperature gradient on the droplet surface. The studies showed that the Marangoni effect has a significant impact on the internal flow. The amplitude of the capillary waves on the surface of the droplet was non-uniform and presented the amplitude characteristics of large-small-some. The wavelength of the capillary waves for burning aviation kerosene droplet ranged from 110 µm to 120 µm.

Effective anticancer nanomedicines need to exhibit prolonged circulation in blood, to extravasate and accumulate in tumours, and to be taken up by tumour cells. These contrasting criteria for persistent circulation and cell-membrane affinity have often led to complex nanoparticle designs with hampered clinical translatability. Here, we show that conjugates of small-molecule anticancer drugs with the polyzwitterion poly(2-( N -oxide- N , N -diethylamino)ethyl methacrylate) have long blood-circulation half-lives and bind reversibly to cell membranes, owing to the negligible interaction of the polyzwitterion with proteins and its weak interaction with phospholipids. Adsorption of the polyzwitterion–drug conjugates to tumour endothelial cells and then to cancer cells favoured their transcytosis-mediated extravasation into tumour interstitium and infiltration into tumours, and led to the eradication of large tumours and patient-derived tumour xenografts in mice. The simplicity and potency of the polyzwitterion–drug conjugates should facilitate the design of translational anticancer nanomedicines. Conjugates of small-molecule anticancer drugs with a polyzwitterion that has negligible interaction with proteins and a weak interaction with phospholipids eradicate large tumours and patient-derived tumour xenografts in mice.

Constipation is one of the most frequent non-motor symptoms of Parkinson disease (PD) and it may be ignored by PD patients, leading to this problem not to be reported in time. The relationships between constipation and demographic variables, motor symptoms and other non-motor symptoms of PD are still unknown. PD patients were evaluated by diagnostic criteria of functional constipation in Rome III and divided into PD with constipation (PD-C) and PD with no constipation (PD-NC) groups. PD patients were assessed by rating scales of motor symptoms and other non-motor symptoms, activity of daily living and quality of life. The frequency of constipation in PD patients was 61.4%, and 24.5% of PD patients had constipation before the onset of motor symptoms. PD-C group had older age and age of onset, longer disease duration, more advanced disease stage, and more severe motor symptoms and non-motor symptoms, including worse cognition and emotion, poorer sleep quality, severer autonomic symptoms, fatigue and apathy. Binary Logistic regression analysis showed that the age, H-Y stage, depression, anxiety and autonomic dysfunction increased the risk of constipation in PD patients. Constipation exerted serious impact on the activity of daily living and quality of life in PD patients.

Food contamination with heavy-metal ions and nitrites poses a serious threat to human health. Consequently, the development of fast and sensitive platforms for detecting these contaminants is urgently needed. In this study, a novel sensing platform was developed by integrating carbon nanotubes generated by the pyrolysis of waste masks (WMCNTs) with ZIF-8 for the simultaneous detection of Cd 2+ , Pb 2+ , and nitrite. Specifically, the electronic structure of the WMCNT backbone was modulated by doping with B and N atoms. Nanoporous ZIF-8 was then grown in-situ on its surface to produce composites with enhanced electrical conductivities and large specific surface areas. This modification provided more active sites for the attachment of heavy-metal ions and nitrites. Under optimized conditions, the sensing platform exhibited a wide linear range with the Pb 2+ , Cd 2+ , and NO 2 − limits of detection of 2.68, 12.12, and 5.94 μM, respectively. Notably, the sensing platform demonstrated excellent anti-interference capabilities and effectively detected nitrites and heavy-metal ions in pickled foods. Graphical abstract

Studies suggest an increased risk of peritonsillar abscess (PTA) recurrence in patients with prior tonsillitis. However, this association is inconsistent and could be confounded by different treatment modalities. This study aimed to assess the risk of recurrence among PTA patients with different degrees of prior tonsillitis and treatment modalities, and the role of tonsillectomy in current practice. All in-patients with peritonsillar abscess between January 2001 and December 2009 were identified in a nationwide, retrospective cohort study. Recurrence was defined as the first occurrence of PTA ≧30 days from the initial PTA. Factors independently associated with recurrence were analyzed using Cox proportional hazard model after adjusting for demographic and clinical data. There were 28,837 patients, with a 5.15% recurrence rate and 4.74 years of follow-up. The recurrence rates were significantly higher among subjects with more than five prior tonsillitis or 1-4 prior tonsillitis compared to those without prior tonsillitis (adjusted hazard ratio, 2.82 [95% confidence interval, 2.39-3.33] and 1.59 [95% CI: 1.38-1.82]). The adjusted HR in patients treated with needle aspiration was 1.08 compared to those treated with incision & drainage (95% CI: 0.85-1.38). After age stratification, the adjusted HRs of more than five prior tonsillitis increased to 2.92 and 3.50 in patients aged ≦18 and 19-29 years respectively. The adjusted HR of needle aspiration only increased in patients ≦18 years old (aHR: 1.98 [95% CI: 0.99-3.97]). The overall tonsillectomy rate was 1.48% during our study period. The risk of PTA recurrence increases with higher degrees of prior tonsillitis in all age groups and management by needle aspiration only in the pediatric population. Patients younger than 30 years old with PTA and more than five prior tonsillitis have the greatest risk of recurrence.

Asparaginase (ASP) is the cornerstone drug in the treatment of extranodal NK/T-cell lymphoma (ENKTCL), and the mechanisms of resistance to ASP remain largely unknown. Long non-coding RNAs play important roles in chemotherapy resistance in various cancers. However, the expression of BCYRN1 and its role in ENKTCL still remain unidentified. Lentivirus-mediated BCYRN1 overexpression and knockdown were performed in SNK-6 cells. Cell autophagy was analyzed by adenovirus expressing GFP-LC3B fusion protein. RNA pull-down and RNA Binding Protein Immunoprecipitation Assay were performed to investigate the relationship between BCYRN1 and p53. Western blot analysis was performed to assess the effect of BCYRN1 on different autophagy pathways. Finally, in vivo xenograft tumor model was constructed to analyze the effect of BCYRN1 on tumor growth and ASP resistance. BCYRN1 was overexpressed in ENKTCL than normal NK cells, and patients with higher expression had significantly inferior progression-free survival (PFS). The IC50 value of ASP was significantly increased in BCYRN1-overexpressed SNK-6 cells and BCYRN1 overexpression could resist the inhibitory effect of ASP on proliferation. ASP could induce concurrent apoptosis and autophagy in ENKTCL, and the latter process was enhanced by overexpression of BCYRN1, mainly through affecting both PI3K/AKT/mTOR and p53/mTOR pathways. BCYRN1 could induce the degradation of p53 via ubiquitination, thus resulting in enhancement of autophagy and ASP resistance, which could be reversed by drug-induced autophagy inhibition. The effect of BCYRN1 on tumor growth and autophagy were confirmed in vivo xenograft model. It was found that BCYRN1 was a valuable prognostic biomarker in ENKTCL. BCYRN1 could promote resistance to ASP by inducing autophagy, which could be reversed by inhibition of autophagy. Our findings highlight the feasibility of combining autophagy inhibition and ASP in the treatment of ENKTCL.

Machine tools may be affected by room temperature, the heat generated by the process, and many other factors. These cause the temperature of the spindle, motor, lead screw, and other parts to rise, and this causes thermal deformation. The main purpose of this study was an exploration of the relationship between the temperature of the spindle and thermal deformation. Measurements were made of the increases in temperature of a CNC lathe spindle, and the related axial displacements involved, at spindle speeds of 1000, 2000, and 3000 rpm. Multiple regression analysis and a general regression neural network were used to establish the relationship between thermal deformation and temperature change individually. The results showed the coefficient of determination of the multiple regression analysis to be 0.9275, while the general regression determined by the neural network was 1. The fitting result of the regression neural network was better than that of multiple regression analysis, and the maximum error was less than 0.1 μm. In addition, this study also used COMSOL simulation analysis software to analyze features of the thermal behavior generated by the spindle structure. A trial and error method was used to adjust the boundary conditions. Results showed that the maximum error in temperature rise determination of simulation and experiment was less than 1 °C.

Purpose: To highlight the knowledge structure and evolutionary trends in research on autophagy in lung cancer. Methods: Research publications on autophagy in lung cancer were retrieved from the Web of Science Core Collection database. VOSviewer and CiteSpace data analysis software were used for the bibliometric and visualization analysis of countries, institutions, authors, journals, and keywords related to this field. Results: From 2013 to 2022, research on autophagy in lung cancer developed rapidly, showing rising trends in annual publications and citations. China (1,986 papers; 48,913 citations), Shandong University (77 publications; 1,460 citations), and Wei Zhang (20 publications; 342 citations) were the most productive and influential country, institution, and author, respectively. The journal with the most publications and citations on autophagy in lung cancer was the International Journal of Molecular Sciences (93 publications; 3,948 citations). An analysis of keyword co-occurrence showed that related research topics were divided into five clusters: 1) Mechanisms influencing autophagy in lung cancer and the role of autophagy in lung cancer; 2) Effect of autophagy on the biological behavior of lung cancer; 3) Regulatory mechanisms of 2 cell death processes: autophagy and apoptosis in lung cancer cells; 4) Role of autophagy in lung cancer treatment and drug resistance; and 5) Role of autophagy-related genes in the occurrence and development of lung cancer. Cell proliferation, migration, epithelial-mesenchymal transition, and tumor microenvironment were the latest high-frequency keywords that represented promising future research directions. Conclusion: This is the first comprehensive study describing the knowledge structure and emerging frontiers of research on autophagy in lung cancer from 2013 to 2022 by means of a bibliometric analysis. The study points to promising future research directions focusing on in-depth autophagy mechanisms, clinical applications, and potential therapeutic strategies, providing a valuable reference for researchers in the field. Systematic Review Registration : [ https://systematicreview.gov/ ], identifier [registration number].

Adenoidectomy in conjunction with tympanostomy tube insertion for treating pediatric otitis media with effusion and recurrent acute otitis media has been debated for decades. Practice differed surgeon from surgeon. This study used population-based data to determine the protective effect of adenoidectomy in preventing tympanostomy tube re-insertion and tried to provide more evidence based information for surgeons when they do decision making. Retrospective birth cohort study. This study used the National Health Insurance Research Database for the period 2000-2009 in Taiwan. The tube reinsertion rate and time to tube re-insertion among children who received tympanostomy tubes with or without adenoidectomy were compared. Age stratification analysis was also done to explore the effects of age. Adenoidectomy showed protective effects on preventing tube re-insertion compared to tympanostomy tubes alone in children who needed tubes for the first time (tube re-insertion rate 9% versus 5.1%, p = 0.002 and longer time to re-insertions, p = 0.01), especially those aged over 4 years when they had their first tube surgery. After controlling the effect of age, adenoidectomy reduced the rate of re-insertion by 40% compared to tympanostomy tubes alone (aHR: 0.60; 95% CI: 0.41-0.89). However, the protective effect of conjunction adenoidectomy was not obvious among children with a second tympanostomy tube insertion. Children who needed their first tube surgery at the age 2-4 years were most prone to have tube re-insertions, followed by the age group of 4-6 years. Adenoidectomy has protective effect in preventing tympanostomy tube re-insertions compared to tympanostomy tubes alone, especially for children older than 4 years old and who needed tubes for the first time. Nonetheless, clinicians should still weigh the pros and cons of the procedure for their pediatric patients.