[Characteristics of resting energy expenditure and evaluation of prediction formulas in young men with different body mass indexes].

OBJECTIVE: To compare the resting energy expenditure (REE) characteristics among young men with different body mass indexes (BMI). METHODS: Thirty young men [average age was (26.93±4.16) years] were enrolled in this study. They underwent resting metabolism tests in the Department of Sports Medicine of Peking University Third Hospital from December 2017 to June 2021. The resting metabolic rate (RMR) was measured by indirect calorimetry, the body composition was measured by bioresistance antibody component analyzer. The REE characteristics were analyzed, and 11 predictive equations were used to estimate RMR and compared with the measured value. The differences were analyzed by paired t-test and intra-class correlation coefficient (ICC). RESULTS: The RMR of the overall 30 young men was (1 960.17±463.11) kcal/d (1 kcal=4.186 8 kJ). Including (1 744.33±249.62) kcal/d in those with normal BMI, which was significantly lower than that in those who were overweight or obese [(2 104.06± 520.32) kcal/d, P < 0.01], but the weight-corrected RMR in those with normal BMI was significantly higher than that in those who were overweight or obese [(24.02±2.61) kcal/(kg·d) vs. (19.98±4.38) kcal/(kg·d), P < 0.01]. The RMR was significantly and positively correlated with body weight, adiposity, lean body mass, body surface area, and extracellular fluid in the subjects with diffe-rent BMI (all P < 0.05). The predicted values of the 11 prediction equations were not in good agreement with the measured values (all ICC < 0.75), with relatively high agreement between the predicted and measured values of the World Health Organization (WHO) equation in overweight obese young men (ICC=0.547, P < 0.01). CONCLUSION: There were significant differences in RMR among young men with different BMI, and the RMR after weight correction should be considered for those who were overweight or obese. The consistency between the predicted values of different prediction equations and the actual measured values of RMR was relatively poor, and it is recommended to accurately measure RMR by indirect calorimetry. For overweight or obese young men, the WHO prediction equation can be considered to calculate RMR, but it is necessary to establish an RMR prediction equation applicable to different BMI populations.

The emerging therapies are reshaping the first-line treatment for advanced hepatocellular carcinoma: a systematic review and network meta-analysis.

Background: Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials. Objectives: The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making. Design: Systematic review and network meta-analysis. Data sources and methods: PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023. Results: After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49-0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3-5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib. Conclusion: Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies. Trial registration: PROSPERO, CRD42022288172.

Lay summary/Key points The efficiency of various systemic therapies in advanced HCC patients with specific characteristics remains to be explored. This study revealed that the efficacy of ICI combined therapies is influenced by factors such as tumor staging, etiology, patient demographics, and more. Additionally, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI combined therapies. Complementing to recent guidelines, this study indicated that several critical factors needed to be took into consideration for patients with advanced HCC.

Engineered M2 macrophage-derived extracellular vesicles with platelet membrane fusion for targeted therapy of atherosclerosis.

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to the formation of plaques rich in lipids. M2 macrophage-derived extracellular vesicles (M2EV) have significant potential for anti-atherosclerotic therapy. However, their therapeutic effectiveness has been hindered by their limited targeting capability in vivo. The objective of this study was to create the P-M2EV (platelet membrane-modified M2EV) using the membrane fusion technique in order to imitate the interaction between platelets and macrophages. P-M2EV exhibited excellent physicochemical properties, and microRNA (miRNA)-sequencing revealed that the extrusion process had no detrimental effects on miRNAs carried by the nanocarriers. Remarkably, miR-99a-5p was identified as the miRNA with the highest expression level, which targeted the mRNA of Homeobox A1 (HOXA1) and effectively suppressed the formation of foam cells in vitro. In an atherosclerotic low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model, the intravenous injection of P-M2EV showed enhanced targeting and greater infiltration into atherosclerotic plaques compared to regular extracellular vesicles. Crucially, P-M2EV successfully suppressed the progression of atherosclerosis without causing systemic toxicity. The findings demonstrated a biomimetic platelet-mimic system that holds great promise for the treatment of atherosclerosis in clinical settings.

Tailoring the Position of Ester Group on N-Alkyl Chains of Benzotriazole-based Small Molecule Acceptors for High-Performance Organic Solar Cells.

Side chain engineering plays a vital role in exploring high-performance small molecule acceptors (SMAs) for organic solar cells (OSCs). In this work, we designed and synthesized a series of A-DA'D-A type SMAs by introducing different N-substituted alkyl and ester alkyl side chains on benzotriazole (BZ) central unit and aimed to investigate the effect of different ester substitution positions on photovoltaic performances. All the new SMAs with ester groups exhibit lower the lowest unoccupied molecular orbital (LUMO) energy levels and more blue-shifted absorption, but relatively higher absorption coefficients than alkyl chain counterpart. After blending with the donor PM6, the ester side chain-based devices demonstrate enhanced charge mobility, reduced amorphous intermixing domain size and long-lived charge transfer state compared to the alkyl chain counterpart, which are beneficial to achieve higher short-circuit current density (Jsc ) and fill factor (FF), simultaneously. Thereinto, the PM6 : BZ-E31 based device achieves a higher power conversion efficiency (PCE) of 18.33 %, which is the highest PCE among the OSCs based on the SMAs with BZ-core. Our work demonstrated the strategy of ester substituted side chain is a feasible and effective approach to develop more efficient SMAs for OSCs.

Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation.

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790-an anti-calcification drug-to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.

Reductive Radical-Polar Crossover Enabled Carboxylative Alkylation of Aryl Thianthrenium Salts with CO2 and Styrenes.

Carboxylic functionalities are among the pivotal groups in bioactive molecules and in the synthesis of new lead compounds because of their unique character in the formation of hydrogen bonds and the possibility of constructing molecular complexes via amide couplings. We adopt the reductive radical-polar crossover strategy to introduce carboxyalkyl groups into arenes with styrenes and CO2 via thianthrenium salts. This protocol exhibits excellent potential as a straightforward and modular platform for site-selective carboxylative derivation of bioactive molecules.

Spiky Artificial Peroxidases with V-O-Fe Pair Sites for Combating Antibiotic-Resistant Pathogens.

With the sharp rise of antibiotic-resistant pathogens worldwide, it is of enormous importance to create new strategies for combating pathogenic bacteria. Here, we create an iron oxide-based spiky artificial peroxidase (POD) with V-O-Fe pair sites (V-Fe2 O3 ) for combating methicillin-resistant Staphylococcus aureus (MRSA). The experimental studies and theoretical calculations demonstrate that the V-Fe2 O3 can achieve the localized "capture and killing" bifunction from the spiky morphology and massive reactive oxygen species (ROS) production. The V-Fe2 O3 can reach nearly 100 % bacterial inhibition over a long period by efficiently oxidizing the lipid membrane. Our wound disinfection results identify that the V-Fe2 O3 can not only efficiently eliminate MRSA and their biofilm but also accelerate wound recovery without causing noticeable inflammation and toxicity. This work offers essential insights into the critical roles of V-O-Fe pair sites and localized "capture and killing" in biocatalytic disinfection and provides a promising pathway for the de novo design of efficient artificial peroxidases.

[Effects of allicin on insulin resistance and free fatty acid levels in obese rats with periodontitis].

PURPOSE: To explore the effects of allicin on insulin resistance and free fatty acids (FFAs) levels in obese rats with periodontitis. METHODS: Forty rats were randomly divided into healthy group, periodontitis group, and low, medium and high dose groups, with 8 rats in each group. The healthy group was healthy rats, and the other groups were induced by sodium glutamate(MSG). After successfully establishing an obesity model, the maxillary molars were ligated and smeared to establish a periodontitis model. Both the periodontitis group and the healthy group were given normal saline, and the allicin low, medium and high dose groups were given allicin 20，40 and 60 mg·kg-1·d-1, mixed with feed for oral administration. After 21 days of treatment, the fasting blood glucose(FPG), fasting insulin (FINS), insulin resistance index (HOMA-IR) scores and FFAs levels of the homeostatic model in rats were detected. The protein expression of TLR4/MyD88 signaling pathway were compared. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: Compared with the healthy group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of the periodontitis group were significantly increased, and the expression of TLR4 and MyD88 proteins was significantly increased(P＜0.05). Compared with the periodontitis group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of low, medium and high-doses groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P＜0.05). Compared with the low-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the middle and high-dose groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P＜0.05). Compared with the middle-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the high-dose group were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P＜0.05). After treatment, FFAs of the low, medium and high-dose groups were significantly lower than those before treatment(P＜0.05). Compared with the healthy group, FFAs levels of the periodontitis group, low-dose and medium-dose groups were significantly increased. Compared with the periodontitis group, FFAs levels of the low, medium and high-dose groups were significantly increased. Compared with the low-dose group, FFAs levels of the high-dose group were significantly increased. Compared with the middle-dose group, FFAs levels of the high-dose group were significantly increased (P＜0.05). CONCLUSIONS: Allicin can improve insulin resistance and obesity in obese rats with periodontitis, and its mechanism of action is related to the TLR4/MyD88 signaling pathway.

1,2-Fluorosulfenylation of unactivated alkenes with thiols and a fluoride source promoted by bromodimethylsulfonium bromide.

A practical method that enables the fluorosulfenylation of unactivated alkenes processed directly with thiols and fluoride salts is presented. Good to excellent efficiencies and functional group tolerance are observed for both alkene substrates and thiols. The procedure also allows the use of gaseous ethylene as a two-carbon building block for ß-fluoro thioether products.

Synthesis of Aryl Thioalkynes Enabled by Electrophilic Sulfenylation of Alkynes and the Following Elimination.

An unexpected deprotonative process of thiirenium ions is presented, which provides a new synthesis of aryl thioalkynes directly from terminal alkynes via the electrophilic activation of the carbon-carbon triple bonds. The conditions are well compatible with various functional-group-substituted aryl alkynes. The direct elimination from the thiirenium ion intermediate, or its tautomer, benzyl vinyl carbocation, is supported by control experiments and labeling reaction.

Effects of Concentrate Feeding Sequence on Growth Performance, Nutrient Digestibility, VFA Production, and Fecal Microbiota of Weaned Donkeys.

In this study, effects on the growth performance, nutrient digestibility, volatile fatty acids (VFA) production, and fecal microbiota of weaned donkeys were observed using different concentrate feeding sequences. Fifteen healthy 6-month-old weaned male donkeys with a body weight of 117.13 ± 10.60 kg were randomly divided into three treatment groups, including group C1 (roughage-then-concentrate), group C2 (concentrate-then-roughage), and group C3 (total mixed ration, TMR). The experiment lasted 35 d. We measured nutrient digestion by the acid-insoluble ash method and analyzed the fecal microbiota of the weaned donkeys by high-throughput sequencing of 16s rRNA genes in the V3-V4 region. The results show that group C3 obtained the best growth performance, and the digestibility of crude protein (CP) and crude extract (EE) was significantly higher than that of group C1 (p < 0.05). Acetic acid, isobutyric acid, valeric acid, isovaleric acid, and caproic acid were notably different among all groups (p < 0.05). In addition, we observed that Firmicutes and Bacteroidetes were dominant in the fecal microbes of each group, and Firmicutes was significantly higher in group C3 (p < 0.05). At the genus level, the different genera were Treponema, Rikenellaceae-RC9-gut-group, Unidentified-F082, and Bacteroidales-RF16-group (p < 0.05). The prediction of fecal microbiota function by PICRUSt indicated that different feeding sequences had minimal impact on the function of the fecal microbiota, particularly on the high-abundance pathway. In summary, the concentrate feeding sequence changed the composition of the fecal microbe of weaned donkeys.

Anisotropic flexibility and rigidification in a TPE-based Zr-MOFs with scu topology.

Tetraphenylethylene (TPE)-based ligands are appealing for constructing metal-organic frameworks (MOFs) with new functions and responsiveness. Here, we report a non-interpenetrated TPE-based scu Zr-MOF with anisotropic flexibility, that is, Zr-TCPE (H4TCPE = 1,1,2,2-tetra(4-carboxylphenyl)ethylene), remaining two anisotropic pockets. The framework flexibility is further anisotropically rigidified by installing linkers individually at specific pockets. By individually installing dicarboxylic acid L1 or L2 at pocket A or B, the framework flexibility along the b-axis or c-axis is rigidified, and the intermolecular or intramolecular motions of organic ligands are restricted, respectively. Synergistically, with dual linker installation, the flexibility is completely rigidified with the restriction of ligand motion, resulting in MOFs with enhanced stability and improved separation ability. Furthermore, in situ observation of the flipping of the phenyl ring and its rigidification process is made by 2H solid-state NMR. The anisotropic rigidification of flexibility in scu Zr-MOFs guides the directional control of ligand motion for designing stimuli-responsive emitting or efficient separation materials.

Integrated analysis of transcriptome and proteome for exploring mechanism of promoting proliferation of equine satellite cells associated with leucine.

The proliferation and differentiation of skeletal muscle satellite cells (SCs) are necessary for the development of mature skeletal muscle. Leucine (Leu) is both an essential amino acid (EAA) and a branched-chain amino acid (BCAA), which has attracted worldwide attention due to its ability to repair and become new fibers. We separated the equine SCs into the control group (CON) and the Leu-supplemented group (LEU), which the cells were cultured in Leu-deprived and Leu-supplemented media respectively. We combined the transcriptome (RNA-Seq) and quantitative proteome (TMT) profiling analyses on proliferation of equine SCs associated with Leu. 1839 up-regulated and 631 down-regulated genes made up the 2470 differentially expressed genes (DEGs), and the 253 differentially abundant proteins (DEPs) included 118 up-regulated and 135 down-regulated proteins. 110 overlapping genes were verified based on the mRNA and protein translation relationship. Moreover, by comparing overlapped pathways through enrichment analysis, we found 13 genes not only appeared among 110 key DEGs/DEPs but also enriched in the KEGG overlapping signaling pathway, including CCL26, STAT2, PCK2, ASNS, GPT2, SHMT2, PHGDH, PGAM2, PSAT1, FTL, HMOX1, STEAP1 and STEAP2. To our knowledge, this is the first report in the world to systematically show how Leu regulated the growth of equine SCs. Leu deficiency inhibits the proliferation of equine SCs and development of fresh muscle fibers was proved in this paper. The main genes in charge of the Leu-induced proliferation of horse SCs have been found. These genes will make it easier to understand the mechanism at work and offer new information for enhancing the performance of sport horses and alleviating the equine muscle damage during exercise in the future.

Stereoselective alkyl C-glycosylation of glycosyl esters via anomeric C-O bond homolysis: efficient access to C-glycosyl amino acids and C-glycosyl peptides.

C-Glycosyl peptides possess excellent metabolic stability and therapeutic properties and thus play critical roles in biological studies as well as drug discoveries. However, the limited accessibility of C-glycosyl amino acids has significantly hindered the broader research of their structural features and mode of action. Herein, for the first time we disclose a novel visible-light-driven radical conjugate addition of 1,4-dihydropyridine (DHP)-derived glycosyl esters with dehydroalanine derivatives, generating C-glycosyl amino acids and C-glycosyl peptides in good yields with excellent stereoselectivities. Redox-active glycosyl esters, as readily accessible and bench-stable radical precursors, could be easily converted to glycosyl radicals via anomeric C(sp3)-O bond homolysis under mild conditions. Importantly, the generality and practicality of this transformation were fully demonstrated in >40 examples including 2-dexosugars, oligosaccharides, oligopeptides, and complex drug molecules. Given its mild reaction conditions, robust sugar scope, and high anomeric control and diastereoselectivity, the method presented herein could find widespread utility in the preparation of C(sp3)-linked sugar-based peptidomimetics.

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway.

AIM: To construct an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion (I/R) injury in 661W cells and the protective effect of ginsenoside Rg1. METHODS: The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro. Apoptosis, intracellular reactive oxygen species (ROS) levels and superoxide dismutase (SOD) levels were measured at different time points during the reperfusion injury process. The injury model was pretreated with graded concentrations of ginsenoside Rg1. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of cytochrome C (cyt C)/B-cell lymphoma-2 (Bcl2)/Bcl2 associated protein X (Bax), heme oxygenase-1 (HO-1), caspase9, nuclear factor erythroid 2-related factor 2 (nrf2), kelch-like ECH-associated protein 1 (keap1) and other genes. Western blot was used to detect the expression of nrf2, phosphorylated nrf2 (pnrf2) and keap1 protein levels. RESULTS: Compared to the untreated group, the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased (P<0.01). Additionally, the ROS content increased and SOD levels decreased significantly (P<0.01). In contrast, treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na2S2O4 treated group (P<0.01). Moreover, Rg1 reduced the levels of caspase3, caspase9, and cytC, while increasing the Bcl2/Bax level. These differences were all statistically significant (P<0.05). Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment, however, Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na2S2O4 treated group (P<0.001). CONCLUSION: The OGD/R process is induced in 661W cells using Na2S2O4. Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway. These results suggest a potential protective effect of Rg1 against retinal I/R injury.

Cardiac Piezo1 Exacerbates Lethal Ventricular Arrhythmogenesis by Linking Mechanical Stress with Ca2+ Handling After Myocardial Infarction.

Ventricular arrhythmogenesis is a key cause of sudden cardiac death following myocardial infarction (MI). Accumulating data show that ischemia, sympathetic activation, and inflammation contribute to arrhythmogenesis. However, the role and mechanisms of abnormal mechanical stress in ventricular arrhythmia following MI remain undefined. We aimed to examine the impact of increased mechanical stress and identify the role of the key sensor Piezo1 in ventricular arrhythmogenesis in MI. Concomitant with increased ventricular pressure, Piezo1, as a newly recognized mechano-sensitive cation channel, was the most up-regulated mechanosensor in the myocardium of patients with advanced heart failure. Piezo1 was mainly located at the intercalated discs and T-tubules of cardiomyocytes, which are responsible for intracellular calcium homeostasis and intercellular communication. Cardiomyocyte-conditional Piezo1 knockout mice (Piezo1Cko) exhibited preserved cardiac function after MI. Piezo1Cko mice also displayed a dramatically decreased mortality in response to the programmed electrical stimulation after MI with a markedly reduced incidence of ventricular tachycardia. In contrast, activation of Piezo1 in mouse myocardium increased the electrical instability as indicated by prolonged QT interval and sagging ST segment. Mechanistically, Piezo1 impaired intracellular calcium cycling dynamics by mediating the intracellular Ca2+ overload and increasing the activation of Ca2+-modulated signaling, CaMKII, and calpain, which led to the enhancement of phosphorylation of RyR2 and further increment of Ca2+ leaking, finally provoking cardiac arrhythmias. Furthermore, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), Piezo1 activation remarkably triggered cellular arrhythmogenic remodeling by significantly shortening the duration of the action potential, inducing early afterdepolarization, and enhancing triggered activity.This study uncovered a proarrhythmic role of Piezo1 during cardiac remodeling, which is achieved by regulating Ca2+ handling, implying a promising therapeutic target in sudden cardiac death and heart failure.

Emerging roles of macrophages in heart failure and associated treatment approaches.

Heart failure is typically caused by different cardiovascular conditions and has a poor prognosis. Despite the advances in treatment in recent decades, heart failure has remained a major cause of morbidity and mortality worldwide. As revealed by in vivo and in vitro experiments, inflammation plays a crucial role in adverse cardiac remodeling, ultimately leading to heart failure. Macrophages are central to the innate immune system, and they are the most indispensable cell type for all cardiac injuries and remodeling stages. The immediate microenvironment regulates their polarization and secretion. In this review, we summarize the phenotypic heterogeneity and governing roles of macrophages in the infarcted, inflamed, and aging heart and assess their significance as potential therapeutic targets in heart failure. We also highlight the current missing links and major challenges in the field that remain to be addressed before macrophages can be exploited for therapeutic applications.

Donkey Oil-Based Ketogenic Diet Prevents Tumor Progression by Regulating Intratumor Inflammation, Metastasis and Angiogenesis in CT26 Tumor-Bearing Mice.

Colon cancer is one of the typical malignant tumors, and its prevalence has increased yearly. The ketogenic diet (KD) is a low-carbohydrate and high-fat dietary regimen that inhibits tumor growth. Donkey oil (DO) is a product with a high nutrient content and a high bioavailability of unsaturated fatty acids. Current research investigated the impact of the DO-based KD (DOKD) on CT26 colon cancer in vivo. Our findings revealed that DOKD administration significantly lowered CT26+ tumor cell growth in mice, and the blood ß-hydroxybutyrate levels in the DOKD group was significantly higher than those in the natural diet group. Western blot results showed that DOKD significantly down-regulated Src, hypoxia inducible factor-1α (HIF-1α), extracellular signal-related kinases 1 and 2 (Erk1/2), snail, neural cadherin (N-cadherin), vimentin, matrix metallopeptidase 9 (MMP9), signal transducer and activator of transcription 3 (STAT3), and vascular endothelial growth factor A (VEGFA), and it significantly up-regulated the expressions of Sirt3, S100a9, interleukin (IL)-17, nuclear factor-kappaB (NF-κB) p65, Toll-like receptor 4 (TLR4), MyD88, and tumor necrosis factor-α. Meanwhile, in vitro validation results showed that LW6 (a HIF-1α inhibitor) significantly down-regulated the expressions of HIF-1α, N-cadherin, vimentin, MMP9, and VEGFA, which supported those of the in vivo findings. Furthermore, we found that DOKD inhibited CT26+ tumor cell growth by regulating inflammation, metastasis, and angiogenesis by activating the IL-17/TLR4/NF-κB p65 pathway and inhibiting the activation of the Src/HIF-1α/Erk1/2/Snail/N-cadherin/Vimentin/MMP9 and Erk1/2/HIF-1α/STAT3/VEGFA pathways. Our findings suggest that DOKD may suppress colon cancer progression and help prevent colon cancer cachexia.

Small-molecule MHC-II inducers promote immune detection and anti-cancer immunity via editing cancer metabolism.

Lack of MHC-II is emerging as a causal factor in cancer immune evasion, and the development of small-molecule MHC-II inducers is an unmet clinical need. Here, we identified three MHC-II inducers, including pristane and its two superior derivatives, that potently induce MHC-II expression in breast cancer cells and effectively inhibit the development of breast cancer. Our data suggest that MHC-II is central in promoting the immune detection of cancer to increase the tumor infiltration of T cells and enhance anti-cancer immunity. By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Collectively, we identified three MHC-II inducers and illustrated that lack of MHC-II caused by hyper-activated fatty acid synthesis to limit immune detection is a potentially widespread mechanism underlying the development of cancer.

Integrating Fly Ash-Controlled Surface Morphology and Candle Grease Coating: Access to Highly Hydrophobic Poly (L-lactic Acid) Composite for Anti-Icing Application.

New ways of recycling fly ash are of great significance for reducing the environmental pollution. In this work, biodegradable hydrophobic poly (L-lactic acid)/fly ash composites for anti-icing application were successfully fabricated via a facile solvent-volatilization-induced phase separation approach. A silane coupling agent of 3-(Trimethoxysilyl) propyl methacrylate was used to decorate a fly ash surface (FA@KH570) for strengthening the interface bonding between fly ash and poly (L-lactic acid). Moreover, FA@KH570 could obviously enhance the crystallinity of poly (L-lactic acid) (PLLA)/FA@KH570 composites, which accelerated the conversion from the liquid-liquid to the liquid-solid phase separation principle. Correspondingly, the controllable surface morphology from smooth to petal-like microspheres was attained simply by adjusting the FA@KH570 content. After coating nontoxic candle grease, the apparent contact angle of 5 wt% PLLA/FA@KH570 composite was significantly increased to an astonishing 151.2°, which endowed the composite with excellent anti-icing property. This strategy paves the way for recycling waste fly ash and manufacturing hydrophobic poly (L-lactic acid) composite for potential application as an anti-icing material for refrigerator interior walls.