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Immune checkpoint blockade therapies targeting the PD-L1/PD-1 axis have demonstrated clear clinical benefits. Improved understanding of the underlying regulatory mechanisms might contribute new insights into immunotherapy. Here, we identify transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) as a modulator of PD-L1 post-translational modifications in tumor cells. Mechanistically, TMUB1 competes with HECT, UBA and WWE domain-containing protein 1 (HUWE1), a E3 ubiquitin ligase, to interact with PD-L1 and inhibit its polyubiquitination at K281 in the endoplasmic reticulum. Moreover, TMUB1 enhances PD-L1 N-glycosylation and stability by recruiting STT3A, thereby promoting PD-L1 maturation and tumor immune evasion. TMUB1 protein levels correlate with PD-L1 expression in human tumor tissue, with high expression being associated with poor patient survival rates. A synthetic peptide engineered to compete with TMUB1 significantly promotes antitumor immunity and suppresses tumor growth in mice. These findings identify TMUB1 as a promising immunotherapeutic target.

Triple-negative breast cancer (TNBC) lacks effective therapeutic targets and has a poor prognosis, easy recurrence and metastasis. It is urgent and important to explore TNBC treatment targets. Through mass spectrometry combined with qRT-PCR validation in luminal A cells and TNBC cells, high-content screening and clinical sample analysis, FUNDC2 was discovered as a novel target. The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear. In this study, we find that FUNDC2 expression in TNBC tissues is significantly higher than that in luminal subtype breast cancer tissues. FUNDC2 silencing in TNBC cells significantly reduces cell proliferation, migration and invasion. As demonstrated in vivo using subcutaneous tumor xenografts in mice, FUNDC2 suppression significantly inhibits tumor growth. The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3β and GLI1, a key factor of the Hedgehog signaling pathway. Therefore, FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC.

Temperature-insensitive elastic modulus known as Elinvar effect is typically achievable in metastable titanium alloys only through thermomechanical processing. Here reports that a directly additively manufactured TiNb-based alloy exhibits Elinvar effect over a wide temperature range of 273 K. This is attributed to its α″+β dual-phase microstructure wherein both the elastic modulus and transition strain of the α″ phase increase monotonically with increasing temperature. The α″ phase was obtained by setting a base-plate temperature of 723 K to act as in-situ aging. This provides a new way to optimize mechanical and functional properties simultaneously by utilizing thermal fields of additive manufacturing. [ABSTRACT FROM AUTHOR]

Nickel slag is the solid waste obtained from the nickel smelting process. Based on the magnetic elements in nickel slag, it is a potential ingredient that could be used in magnetic compound fluid (MCF) polishing. This work discusses polishing in MCF using nickel slag and modified slag. Investigations are conducted into how MCF is affected by the amount of modified slag and nickel slag present during polishing. The connections between shear force, position, material removal rate, morphological characteristics, and polishing quality are covered. Nickel slag is mixed with CaO, the alkalinity is adjusted, and the mixture is heated to 1500 °C to fully melt and oxidize it. The resulting product is modified slag. The morphological changes in MCF slurry before and after polishing were examined using an industrial camera, and the effect of different MCF slurry components on polishing performance was analyzed throughout the polishing process. In addition, the positioning of modified slag within the magnetic cluster formed during the polishing process was determined through a scanning electron microscope and by energy dispersive x-ray spectroscopy mapping of MCF slurry. The aforementioned research establishes the polishing mechanism for nickel slag and modified slag. The experimental results indicate that the polishing effect of the experimental group with added modified slag is better than that of added nickel slag. Under the same conditions, the surface roughness was reduced by 60% when modified slag was used instead of nickel slag. It was found that the optimal process is where the modified slag content is 10%, where the material removal rate is 1.207 × 108µm3/min and the surface roughness decrease rate is 95.482%. The polishing shear force is around 2.7N, which is twice as much as that of nickel slag. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the characteristics of polysomnography （PSG） in depression patients complicating moderate-to-severe obstructive sleep apnea hypopnea syndrome （OSAHS）.MethodsA retrospective analysis was conducted on the outpatients， inpatients and physical examination population who completed overnight PSG monitoring in the sleep medicine center of Suzhou Guangji Hospital from December 2017 to October 2019. Four groups of subjects were finally enrolled， including depression patients with moderate-to-severe OSAHS （n=31）， depression patients without OSAHS （n=79）， moderate-to-severe OSAHS patients （n=96） and normal control group （n=32）. The sleep process related indicators （total sleep time， sleep latency， number of awakenings）， sleep structure related indicators （N1， N2， N3， percentage of REM sleep， REM latency， REM sleep duration）， sleep-related respiratory variables （oxygen reduction index） and other polysomnographic parameters of the four groups were compared.ResultsIn terms of sleep process， the total sleep time， sleep latency and number of awakenings yielded significant differences among the four groups （F=2.874， 3.959， 12.291， P

Background: Limited data were available to understand the significance of ferroptosis in leukemia prognosis, regardless of the genomic background. Methods: RNA-seq data from 151 AML patients were analyzed from The Cancer Genome Atlas (TCGA) database, along with 70 healthy samples from the Genotype-Tissue Expression (GTEx) database. Ferroptosis-related genes (FRGs) features were constructed by multivariate COX regression analysis and risk scores were calculated for each sample and a novel prediction model was identified. The validation was carried out using data from 35 AML patients and 13 healthy controls in our cohort. Drug sensitivity analysis was conducted on various chemotherapeutic drugs. Results: A signature of 10 FRGs was identified, as prognostic predictors for AML, and the risk scores were calculated to constructed the prognostic features of FRGs. Significantly lower overall survival was observed in the high-risk group. The predictive ability of these features for AML prognosis was confirmed using Cox regression analysis, ROC curves, and DCA. The prediction model performed well in our clinical practices, and had its potential superiority when comparing to classical NCCN risk stratification. Multiple chemotherapy drugs, including paclitaxel, dactinomycin, cisplatin, etc. had a lower IC50 in FRGs high-risk group than low-risk group. Conclusion: The AML prognosis model based on FRGs accurately predicts AML prognosis and drug sensitivity, and the drugs identified worthy further investigation. [ABSTRACT FROM AUTHOR]

Background: Perianal infection has a high incidence and mortality rate in patients with acute myeloid leukemia (AML). Sometimes there is a lack of effective anti-infective treatment regimens. Case Presentation: A 58-year-old male diagnosed with AML presented with secondary perianal infection and septic shock upon admission. Although multiple pathogen cultivation and antibiotic sensitivity tests indicated the presence of sensitive strains, the corresponding antibiotics were ineffective. As a last resort, carrimycin was introduced, ultimately controlling the infection and leading to disease remission. Conclusion: Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation. [ABSTRACT FROM AUTHOR]