IL-1ß-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance.

Interleukin-1ß (IL-1ß) is a key protein in inflammation and contributes to tumor progression. However, the role of IL-1ß in cancer is ambiguous or even contradictory. Here, we found that upon IL-1ß stimulation, nicotinamide nucleotide transhydrogenase (NNT) in cancer cells is acetylated at lysine (K) 1042 (NNT K1042ac) and thereby induces the mitochondrial translocation of p300/CBP-associated factor (PCAF). This acetylation enhances NNT activity by increasing the binding affinity of NNT for NADP+ and therefore boosts NADPH production, which subsequently sustains sufficient iron-sulfur cluster maintenance and protects tumor cells from ferroptosis. Abrogating NNT K1042ac dramatically attenuates IL-1ß-promoted tumor immune evasion and synergizes with PD-1 blockade. In addition, NNT K1042ac is associated with IL-1ß expression and the prognosis of human gastric cancer. Our findings demonstrate a mechanism of IL-1ß-promoted tumor immune evasion, implicating the therapeutic potential of disrupting the link between IL-1ß and tumor cells by inhibiting NNT acetylation.

Aberrant overexpression of myosin 1b in glioblastoma promotes angiogenesis via VEGF-myc-myosin 1b-Piezo1 axis.

Glioblastoma (GBM) is the most aggressive intracranial malignancy with poor prognosis. Enhanced angiogenesis is an essential hallmark of GBM, which demonstrates extensive microvascular proliferation and abnormal vasculature. Here, we uncovered the key role of myosin 1b in angiogenesis and vascular abnormality in GBM. Myosin 1b is upregulated in GBM endothelial cells (ECs) compared to the paired non-malignant brain tissue. In our study, we found that myosin 1b promotes migration, proliferation and angiogenesis of human/mouse brain ECs. We also found that myosin 1b expression in ECs can be regulated by vascular endothelial growth factor (VEGF) signaling through myc. Moreover, myosin 1b promotes angiogenesis via Piezo1 by enhancing Ca2+ influx, in which process VEGF can be the trigger. In conclusion, our results identified myosin 1b as a key mediator in promoting angiogenesis via mechanosensitive ion channel component 1 (Piezo1) and suggested that VEGF/myc signaling pathway could be responsible for driving the changes of myosin 1b overexpression in GBM ECs.

Inhibition of mitochondrial citrate shuttle alleviates metabolic syndromes induced by high-fat diet.

The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on SLC25A1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of SLC25A1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for 4 wk, whereas Nile tilapia received intraperitoneal injections of dsRNA to knock down slc25a1b for 7 days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Of note, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride (TAG) accumulation by deacetylating carnitine palmitoyltransferase 1a (Cpt1a). In addition, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of nonhistone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD.NEW & NOTEWORTHY The mitochondrial citrate shuttle is a crucial physiological process for maintaining metabolic homeostasis. In the present study, we found that inhibition of mitochondrial citrate shuttle (Slc25a1) could alleviate metabolic syndromes induced by high-fat diet (HFD) through remodeling hepatic protein acetylation modification. Briefly, Slc25a1 inhibition reduces hepatic triglyceride deposition by deacetylating Cpt1a and reduces glucose oxidative catabolism by acetylating Pdhe1α. Our study provides new insights into the treatment of diet-induced metabolic syndromes.

Extracellular vesicle encapsulated Homer1a as novel nanotherapeutics against intracerebral hemorrhage in a mouse model.

Homer1a and A2 astrocytes are involved in the regulation of inflammation induced by intracerebral hemorrhage (ICH). However, there is no anticipated treatment strategy based on the anti-inflammatory effect of Homer1a and A2 astrocytes. Here, we successfully induced A2 astrocytes in vitro, and then we report an efficient method to prepare Homer1a+ EVs derived from A2 astrocytes which making it more stable, safe, and targetable to injured neurons. Homer1a+ EVs promotes the conversion of A1 to A2 astrocytes in ICH mice. Homer1a+ EVs inhibits activation and nuclear translocation of NF-κB, thereby regulating transcription of IL-17A in neurons. Homer1a+ EVs inhibits the RAGE/NF-κB/IL-17 signaling pathway and the binding ability of IL-17A: IL17-AR and RAGE: DIAPH1. In addition, Homer1a+ EVs ameliorates the pathology, behavior, and survival rate in GFAPCreHomer1fl/-Homer1a± and NestinCreRAGEfl/fl ICH mice. Our study provides a novel insight and potential for the clinical translation of Homer1a+ EVs in the treatment of ICH.

SiPM joint likelihood reception for mobile LED-optical communication under pointing errors.

Light-emitting diode (LED)-optical communication is a novel spectrum communication with wide field of view (FOV), light weight, and long-distance free-space capabilities. Due to atmospheric turbulence attenuation and pointing errors caused by long-distance communication, this Letter proposes a multi-pixel channel joint maximum likelihood (JML) reception method using a highly sensitive silicon photomultiplier (SiPM). To evaluate the performance of the SiPM under mobile terminal jittering communication, we analyze the effect of optical transmitting power, pointing errors, and signal-to-noise ratio (SNR) gain on optical communication by comparing JML with signal channel using the maximum likelihood (ML) algorithm. Both simulation analysis and experimental results demonstrate that the proposed JML algorithm to process signals received from SiPM multi-pixel channels can effectively mitigate the impact of pointing errors on the bit error rate (BER) of optical communications by two orders of magnitude at large jitter radians and SNR.

Mobile recognition and positioning for multiple visible light communication cells using a convolutional neural network: publisher's note.

This publisher's note contains a correction to Opt. Lett.48, 6468 (2024)10.1364/OL.503007.

Healthy lifestyles, systemic inflammation and breast cancer risk: a mediation analysis.

BACKGROUND: Despite the known association between healthy lifestyles and reduced risk of breast cancer, it remains unclear whether systemic inflammation, as a consequence of unhealthy lifestyles, may mediate the association. METHODS: A cohort study of 259,435 female participants in the UK Biobank was conducted to estimate hazard ratio (HR) for breast cancer according to 9 inflammation markers using Cox regression models. We further estimated the percentage of total association between healthy lifestyle index (HLI) and breast cancer that is mediated by these inflammation markers. RESULTS: During 2,738,705 person-years of follow-up, 8,889 cases of breast cancer were diagnosed among 259,435 women in the UK Biobank cohort. Higher level of C-reactive protein (CRP), systemic immune-inflammation index (SII), CRP-to-albumin Ratio (CAR), CRP-to-lymphocyte Ratio (CLR), monocyte-to-HDL-c ratio (MHR), and neutrophil-to-HDL-c ratio (NHR) were associated with increased breast cancer risk, while a higher lymphocyte-to-monocyte ratio (LMR) was associated with a lower risk. The inverse association between HLI and breast cancer was weakly mediated by CRP (8.5%), SII (1.71%), CAR (8.66%), CLR (6.91%), MHR (6.27%), and NHR (7.33%). When considering individual lifestyle factors, CRP and CAR each mediated 16.58% and 17.20%, respectively, of the associations between diet score and breast cancer risk, while the proportion mediated for physical activity and breast cancer were 12.13% and 11.48%, respectively. Furthermore, MHR was found to mediate 13.84% and 12.01% of the associations between BMI, waist circumference, and breast cancer. CONCLUSION: The association of HLI and breast cancer is weakly mediated by the level of inflammation, particularly by CRP and CAR. Systemic inflammatory status may be an intermediate in the biological pathway of breast cancer development.

Glymphatic System in Preterm Neonates: Developmental Insights Following Birth Asphyxia.

BACKGROUND: Birth asphyxia (BA) and germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are common clinical events in preterm neonates. However, their effects on the glymphatic system (GS) development in preterm neonates remain arcane. PURPOSE: To evaluate the developmental trajectory of the GS, and to investigate the effects of BA and GMH-IVH on GS function in preterm neonates. STUDY TYPE: Prospective. POPULATION: Two independent datasets, prospectively acquired internal dataset (including 99 preterm neonates, 40 female, mean [standard deviation] gestational age (GA) at birth, 29.95 [2.63] weeks) and the developing Human Connectome Project (dHCP) dataset (including 81 preterm neonates, 29 female, median [interquartile range] GA at birth, 32.71 [4.28] weeks). FIELD STRENGTH/SEQUENCE: 3.0 T MRI and diffusion-weighted spin-echo planar imaging sequence. ASSESSMENT: The diffusion-weighted images were preprocessed in volumetric space using the FMRIB Software Library and diffusion along the perivascular space (DTI-ALPS) index was accessed to evaluate GS function. STATISTICAL TESTS: Two sample t tests, one-way analysis of variance followed by least-significant difference (LSD) post hoc analysis, chi-squared tests, and Pearson's correlation analysis. Significance level: P < 0.05. RESULTS: In prospectively acquired internal dataset, preterm neonates with BA exhibited a significant lower DTI-ALPS index than those without BA (0.98 ± 0.08 vs. 1.08 ± 0.07, T = -5.89); however, GMH-IVH did not exert significant influences on the DTI-ALPS index (P = 0.83 and 0.27). The DTI-ALPS index increased significantly at postmenstrual age ranging from 25 to 34 weeks (r = 0.38) and then plateaued after 34 weeks (P = 0.35), which we also observed in the dHCP dataset. DATA CONCLUSION: BA rather than GMH-IVH serves as the major influencing factor in the development of GS in preterm neonates. Moreover, as GS development follows a nonlinear trajectory, we recommend close monitoring of GS development in preterm neonates with a GA less than 34 weeks. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

The interaction of diet, alcohol, genetic predisposition, and the risk of breast cancer: a cohort study from the UK Biobank.

BACKGROUND: Dietary factors have consistently been associated with breast cancer risk. However, there is limited evidence regarding their associations in women with different genetic susceptibility to breast cancer, and their interaction with alcohol consumption is also not well understood. METHODS: We analyzed data from 261,853 female participants in the UK Biobank. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between dietary factors and breast cancer risk. Additionally, we assessed the interaction of dietary factors with alcohol consumption and polygenic risk score (PRS) for breast cancer. RESULTS: A moderately higher risk of breast cancer was associated with the consumption of processed meat (HR = 1.10, 95% CI 1.03, 1.18, p-trend = 0.016). Higher intake of raw vegetables and fresh fruits, and adherence to a healthy dietary pattern were inversely associated with breast cancer risk [HR (95% CI):0.93 (0.88-0.99), 0.87 (0.81, 0.93) and 0.93 (0.86-1.00), p for trend: 0.025, < 0.001, and 0.041, respectively]. Furthermore, a borderline significant interaction was found between alcohol consumption and the intake of processed meat with regard to breast cancer risk (P for interaction = 0.065). No multiplicative interaction was observed between dietary factors and PRS. CONCLUSION: Processed meat was positively associated with breast cancer risk, and vegetables, fruits, and healthy dietary patterns were negatively associated with breast cancer risk. We found no strong interaction of dietary factors with alcohol consumption and genetic predisposition for risk of breast cancer.

An active controllable wide-angle and ultra-wideband terahertz absorber/reflector based on VO2 metamaterial.

The use of metamaterials in the design of optics is an important strategy for controlling light fields. Numerous terahertz metamaterial devices have been recently designed; however, their performance is relatively limited. Here, the thermally induced phase change characteristics of vanadium dioxide (VO2) were harnessed to design a perfect wide-angle and ultra-wideband switchable terahertz absorber/reflector with a simple structure and three layers from top to bottom (VO2, SiO2, and Au). The absorption mechanism based on the impedance matching theory and electric field distribution was investigated, and the influence of structural parameters on the absorption rate and performance of the absorber in a wide wave vector range were analyzed. The study findings showed that the device perfectly absorbed a bandwidth of over 6.0 THz (absorption >90%). The absorption (reflection) was modulated from 0.01 to 0.999 with the change of the background temperature. More importantly, the device could switch between complete ultra-wideband reflection and perfect absorption over a wide angle range. This study provides important insights into the design of terahertz functional devices.