Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme OXCT1. We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in hepatocellular carcinoma in vivo, we conducted multiplex immunohistochemistry (mIHC) experiments on human HCC specimens. To explore the role of OXCT1 in mouse hepatocellular carcinoma tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4 trimethylation (H3K4me3) level in the Arg1 promoter. In addition, Pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreasing CD8+ T-cell exhaustion and deceleration of tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in HCC patients. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping HCC progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for HCC. Here, we found that ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. And the strategic pharmacological intervention or genetic downregulation of OXCT1 in TAMs enhances the antitumor immunity and decelerated tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer.

Glycine-Ti3C2Tx Hybrid Material Improves the Electrochemical Corrosion Resistance of a Water-Borne Epoxy Coating.

Improving the dispersibility and compatibility of nanomaterials in water-borne epoxy resins is an important means to improve the protection ability and corrosion resistance of coatings. In this study, glycine-functionalized Ti3C2Tx (GT) was used to prepare an epoxy composite coating. The results of Fourier transform infrared spectroscopy and X-ray diffraction showed that glycine was successfully modified. The scanning electron microscopy and transmission electron microscopy results showed that the aggregation of Ti3C2Tx was alleviated. Electrochemical impedance spectroscopy test results show that, after 60 days of immersion, GT coating still shows the best protection performance, and the composite coating |Z|f = 0.01 Hz is 3 orders of magnitude higher than that of the pure epoxy coating. This is mainly because, after adding glycine, the -COOH group on the surface of glycine binds to the -OH group on the surface of Ti3C2Tx, improving the aggregation of Ti3C2Tx itself. At the same time, the -NH group of glycine can also participate in the curing reaction of epoxy resin to strengthen the bonding strength between the coating and the metal. The good dispersion of GT in epoxy resin makes it fill the pores and holes left by epoxy resin curing and strengthen the corrosion resistance. The easy availability and green properties of glycine provide a simple and environmentally friendly method for the modification of Ti3C2Tx.

Solar Azo-Switches for Effective E→Z Photoisomerization by Sunlight.

Natural photoactive systems have evolved to harness broad-spectrum light from solar radiation for critical functions such as light perception and photosynthetic energy conversion. Molecular photoswitches, which undergo structural changes upon light absorption, are artificial photoactive tools widely used for developing photoresponsive systems and converting light energy. However, photoswitches generally need to be activated by light of specific narrow wavelength ranges for effective photoconversion, which limits their ability to directly work under sunlight and to efficiently harvest solar energy. Here, focusing on azo-switches-the most extensively studied photoswitches, we demonstrate effective solar E→Zphotoisomerization with photoconversions exceeding 80% under unfiltered sunlight. These sunlight-driven azo-switches are developed by rendering the absorption of E isomers overwhelmingly stronger than that of Z isomers across a broad ultraviolet to visible spectrum. This unusual type of spectral profile is realized by a simple yet highly adjustable molecular design strategy, enabling the fine-tuning of spectral window that extends light absorption beyond 600 nm. Notably, back-photoconversion can be achieved without impairing the forward solar isomerization, resulting in unique light-reversible solar switches. Such exceptional solar chemistry of photoswitches provides unprecedented opportunities for developing sustainable light-driven systems and efficient solar energy technologies.

Nomograms Predict PFS and OS for SCLC Patients After Standardized Treatment: A Real-World Study.

Purpose: This study aims to investigate the process of small cell lung cancer (SCLC) patients from achieving optimal efficacy to experiencing disease progression until death. It examines the predictive value of the treatment response on progression free survival (PFS) and overall survival (OS) of SCLC patients. Patients and Methods: We conducted a retrospective analysis on 136 SCLC patients diagnosed from 1992 to 2018. Important prognostic factors were identified to construct nomogram models. The predictive performance of the models was evaluated using the receiver operating characteristic curves and calibration curves. Survival differences between groups were compared using Kaplan-Meier survival curves. Subsequently, an independent cohort consisting of 106 SCLC patients diagnosed from 2014 to 2021 was used for validation. Results: We constructed two nomograms to predict first-line PFS (PFS1) and OS of SCLC. The area under the receiver operating characteristic curves for the PFS1 nomogram predicting PFS at 3-, 6-, and 12-months were 0.919 (95% CI: 0.867-0.970), 0.908 (95% CI: 0.860-0.956) and 0.878 (95% CI: 0.798-0.958), and for the OS nomogram predicting OS at 6-, 12-, and 24-months were 0.814 (95% CI: 0.736-0.892), 0.819 (95% CI: 0.749-0.889) and 0.809 (95% CI: 0.678-0.941), indicating those two models with a high discriminative ability. The calibration curves demonstrated the models had a high degree of consistency between predicted and observed values. According to the risk scores, patients were divided into high-risk and low-risk groups, showing a significant difference in survival rate. And these findings were validated in another independent validation cohort. Conclusion: Based on the patients' treatment response after standardized treatment, we developed and validated two nomogram models to predict PFS1 and OS of SCLC. The models demonstrated good accuracy, reliability and clinical applicability by validating in an independent cohort.

Metabolomic analysis of rumen-protected branched-chain amino acids in primiparous dairy cows.

Introduction: Peripartal cows are susceptible to a negative energy balance due to inadequate nutrient intake and high energy requirements for lactation. Improving the energy metabolism of perinatal dairy cows is crucial in increasing production in dairy cows. Methods: In this study, we investigated the impact of rumen-protected branched-chain amino acid (RPBCAA) on the production performance, energy and lipid metabolism, oxidative stress, and immune function of primiparous dairy cows using metabolomics through a single-factor experiment. Twenty healthy primiparous Holstein cows were selected based on body condition scores and expected calving date, and were randomly divided into RPBCAA (n = 10) and control (n = 10) groups. The control group received a basal diet from calving until 21 d in milk, and the RPBCAA group received the basal diet and 44.6 g/d RPLeu, 25.14 g/d RPIle, and 25.43 g/d RPVal. Results: In comparison to the control group, the supplementation of RPBCAA had no significant effect on milk yield and milk composition of the dairy cows. Supplementation with RPBCAA significantly increased the concentrations of insulin, insulin growth factor 1, glucagon, and growth hormones, which are indicators of energy metabolism in postpartum cows. The very low density lipoprotein, fatty acid synthase, acetyl coenzyme A carboxylase, and hormone-sensitive lipase contents of the RPBCAA group were significantly greater than that of the control group; these metrics are related to lipid metabolism. In addition, RPBCAA supplementation significantly increased serum glutathione peroxidase and immunoglobulin G concentrations and decreased malondialdehyde concentrations. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed 414 serum and 430 milk metabolic features. Supplementation with RPBCAA primarily increased concentrations of amino acid and lipid metabolism pathways and upregulated the abundance of serotonin, glutamine, and phosphatidylcholines. Discussion: In summary, adding RPBCAA to the daily ration can influence endocrine function and improve energy metabolism, regulate amino acid and lipid metabolism, mitigate oxidative stress and maintain immune function on primiparous cows in early lactation.

Improving Copper Active Site Speciation on Cu-Ce/SSZ-13 for Ammonia Oxidation via Si/Al Ratio Modulation.

Catalytic oxidation is a promising purification technique for ammonia (NH3) emission. However, high ignition temperatures and NOx peroxide generation limit its effectiveness due to a lack of active sites. Herein, the effects of Si/Al ratio (SAR) modulation on the speciation of copper active sites and the reaction mechanism at different acidic sites were investigated by loading CuO-CeO2 onto SSZ-13 with different SARs (Cu-Ce/SAR15, 20, and 30). Among them, Cu-Ce/SAR20 exhibits the lowest induction temperature (T20 = 180 °C) and the highest nitrogen selectivity (above 95%), attributing to a higher number of Cu2+ exchange sites. In situ IR spectroscopy and isotopic (18O2) transient response experiments indicate that more active Cu2+ in Cu-Ce/SAR20 provides sufficient Lewis acidic sites for NH3 adsorption and favors the stability of Si-OH-Al structures (Brønsted acid sites). NH3 adsorbed at Lewis acidic sites tends to form peroxide byproducts (NOx), while the NH4+ adsorbed at Brønsted acidic sites generates the key intermediate NH4NO2, which decomposes to N2 at high temperatures, thus enhancing nitrogen selectivity. The whole process mainly follows the Mars-van Krevelen (M-K) mechanism, with the Langmuir-Hinshelwood (L-H) mechanism playing a supporting role. Z2Cu2+ coordinates with adjacent Al atoms within the six-membered ring (6MR) and undergoes a slight deformation at high temperatures, facilitating the migration of the lattice oxygen. SAR plays a crucial role in local environmental speciation of reactive Cu2+, where the sufficient isolated Al provided in SAR20 pulls Cu2+ into the eight-membered ring (8MR), allowing it to come into contact with NH3 more readily.

Outcomes Following Different Management of Mycotic Infrarenal Abdominal Aortic Aneurysms.

OBJECTIVE: The objective was to present our experience on managing mycotic infrarenal abdominal aortic aneurysm (MIAAA) through a retrospective cohort study. METHODS: Data of patients with MIAAA managed in our center from July 2016 to October 2022 were retrospectively analyzed. The diagnosis of MIAAA was made based on: (1) preoperative clinical signs of infection; (2) elevated serologic infection parameters; (3) para-aneurysmal infection features on enhanced computed tomography; and (4) positive blood or tissue cultures. All the patients received standard antibiotic therapy. Surgical management including endovascular aneurysm repair (EVAR), initial EVAR followed by open re-operation, and initial open surgical repair (OSR) were conducted according to disease seriosity, physical condition, and patient's will. Infection index and clinical outcome were evaluated during the follow-up time. RESULTS: A total of 23 patients (21 men; averaged=66.3 years, range=49-79 years) were included, with a mean follow-up time of 19.9 months (range=1-75 months). Bacteria culture from blood or tissue specimen was positive in 15 patients (Salmonella, n=8; Escherichia coli, n=3; methicillin-sensitive Staphylococcus aureus [MSSA], n=1; Klebsiella pneumoniae, n=1; Staphylococcus epidermidis, n=1; Mycobacterium tuberculosis, n=1). Seven patients received OSR as the initial surgical intervention, whereas 14 patients chose EVAR instead. The 2 conservatively managed patients (refused surgery) died within 30 days. The 7 patients who received initial OSR survived till now. Among the 14 patients who underwent initial EVAR, infection deteriorated without exception (14/14, 100%). Three of these patients refused re-operation and died within 6 months. Eleven patients received secondary surgical intervention (10 cases of aneurysm and endograft resection, thorough debridement, subclavian to bi-femoral artery bypass, or in situ aorta reconstruction; 1 case of laparoscopic debridement) and 7 survived the follow-up time. The overall mortality rate was 39.1% (9/23). The mortality rates differed greatly following different intervention methods (merely antibiotic management, 100%; initial open operation, 0%; initial EVAR without secondary operation, 100%; initial EVAR plus secondary operation, 36.4%). CONCLUSIONS: Open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely EVAR is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary OSR. CLINICAL IMPACT: The management of mycotic or primary-infected aortic aneurysm is challenging; treatment remains controversial. Our center has reviewed our experience over the past 6 years and found that open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely endovascular aneurysm repair (EVAR) is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary open surgical repair.

Increased regional body fat is associated with depressive symptoms: a cross-sectional analysis of NHANES data obtained during 2011-2018.

AIMS: The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study included 3393 participants aged ≥ 20 years from the NHANES performed during 2011-2018. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The fat mass (FM) was measured in different regions using dual-energy X-ray absorptiometry to determine the total FM, trunk FM, arm FM, and leg FM. The FM index (FMI) was obtained by dividing the FM in kilograms by the square of the body height in meters. Weighted data were calculated in accordance with analytical guidelines. Linear logistic regression models were used to quantify the association between regional FMI and depressive symptoms. Univariate and stratified analyses were also performed. RESULTS: The participants in this study comprised 2066 males and 1327 females. There were 404 (11.91%) participants with depressive symptoms, who were aged 40.89 ± 11.74 years and had a body mass index of 30.07 ± 7.82 kg/m². A significant association was found between total FMI and depressive symptoms. In the fully adjusted multivariate regression model, a higher total FMI (odds ratio = 2.18, 95% confidence interval [CI] = 1.08-4.39) was related to a higher risk of depressive symptoms, while increased total FMI (ß = 1.55, 95% CI = 0.65-2.44, p = 0.001), trunk FMI (ß = 0.57, 95% CI = 0.04-1.10, p = 0.036), and arm FMI (ß = 0.96, 95% CI = 0.33-1.59, p = 0.004) were significantly associated with PHQ-9 (Patient Health Questionnaire-9) scores, whereas the leg FMI was not (p = 0.102). The weighted association between total FMI and depressive symptoms did not differ significantly between most of the subpopulations (all p values for interaction > 0.05). The risk of having depression was higher in individuals who were non-Hispanic Whites, smokers, drinkers, obese, and had diabetes and thyroid problems (p < 0.05). CONCLUSION: These findings suggest that the population with a higher regional FMI is more likely to have depressive symptoms, especially in those who also have an increased total FMI. The association is more pronounced in individuals who are smokers, drinkers, obese, and have diabetes and thyroid problems.

Effect of Stress Relief on Coal Seam Gas Migration: Experiment and Application Discussion.

Stress relief-induced enhanced permeability is one of the crucial measures for promoting gas desorption flow and strengthening gas extraction. In order to examine the impact of stress relief and its magnitude on gas migration, this article explores the gas desorption flow during the stress relief process and elucidates the influence of stress relief degree on gas extraction. The results indicate that considering the analysis of the pore structure effect on gas seepage, the four coal samples' permeability is ranked as PDS > CSL > JZS > GHS. Throughout the stress relief process, the gas desorption rates of different coal samples under various stress paths exhibit varying degrees of increase. As an illustration, following 3600 s of stress alterations, the gas desorption rate of CSL1# experiences a notable increase, surging by 2.57 times; PDS2# shows 55.93 times increase after 4200 s, and JZS3# exhibits 3.13 times increase after 5400 s. A stress relief degree model is established to investigate the variation of horizontal stress and stress relief degrees under different borehole spacings, vertical stresses, cohesion, and internal friction angles for various borehole diameters (coal output). Optimal stress relief is achieved with a borehole diameter greater than 1.52 m with a borehole spacing set at 4 m. When the stress relief degree exceeds 30%, the corresponding borehole diameter ranges for different vertical stresses are 1.49-1.6 m. Similarly, for cohesion, the ranges are 1.25-1.68 m, and for internal friction angles, the ranges are 1.39-1.53 m. The research results can provide valuable insights for determining parameters in the on-site construction of stress relief boreholes.

Artificial intelligence to automate assessment of ocular and periocular measurements.

PURPOSE: To develop and validate a deep learning facial landmark detection network to automate the assessment of periocular anthropometric measurements. METHODS: Patients presenting to the ophthalmology clinic were prospectively enrolled and had their images taken using a standardised protocol. Facial landmarks were segmented on the images to enable calculation of marginal reflex distance (MRD) 1 and 2, palpebral fissure height (PFH), inner intercanthal distance (IICD), outer intercanthal distance (OICD), interpupillary distance (IPD) and horizontal palpebral aperture (HPA). These manual segmentations were used to train a machine learning algorithm to automatically detect facial landmarks and calculate these measurements. The main outcomes were the mean absolute error and intraclass correlation coefficient. RESULTS: A total of 958 eyes from 479 participants were included. The testing set consisted of 290 eyes from 145 patients. The AI algorithm demonstrated close agreement with human measurements, with mean absolute errors ranging from 0.22 mm for IPD to 0.88 mm for IICD. The intraclass correlation coefficients indicated excellent reliability (ICC > 0.90) for MRD1, MRD2, PFH, OICD, IICD, and IPD, while HPA showed good reliability (ICC 0.84). The landmark detection model was highly accurate and achieved a mean error rate of 0.51% and failure rate at 0.1 of 0%. CONCLUSION: The automated facial landmark detection network provided accurate and reliable periocular measurements. This may help increase the objectivity of periocular measurements in the clinic and may facilitate remote assessment of patients with tele-health.

Analysis of Factors Associated with Anterior Location of Marx's Line.

PURPOSE: The study aimed to investigate the factors associated with anterior location of Marx's line in ocular surface and living habits, especially in tear film. MATERIALS AND METHODS: This cross-sectional study enlisted 483 participants with meibomian gland dysfunction, who were divided into two groups: 160 participants with mild anterior location of Marx's line and 323 participants with moderate-to-severe anterior location. Participants completed a survey of demographic characteristics (sex, age, length of visual terminal use, sleep duration, skin property), and the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires. They also underwent slit-lamp examinations of the lids, and measurements of non-invasive tear break up time, tear meniscus height, fluorescein tear break up time, lipid layer thickness, partial blink rate, lid wiper epitheliopathy, and meibomian gland dropout. RESULTS: The tear meniscus height (mild:0.21(0.18-0.25), moderate-to-severe:0.19(0.16-0.23), p = 0.004), fluorescein tear break up time(mild:3(2-4),moderate to severe:2(1-3), p = 0.000), max LLT(mild:87(62-100), moderate-to-severe:99(69-100), p = 0.04), average LLT(mild:64.5(47.5-96.75), moderate-to-severe:74(53-100), p = 0.012), min LLT(mild:52(38-75), moderate-to-severe:59(41-85), p = 0.029) differed significantly between mild and moderate-to-severe anterior location of Marx's line, and associated to the anterior location of Marx's line(r=-0.134, p = 0.03; r=-0.194, p = 0.000; r = 0.093, p = 0.041; r = 0.119, p = 0.009; r = 0.105, p = 0.022) However, no statistical significance was observed in the OSDI, SPEED, partial blink rate, non-invasive tear breakup time, lipid layer thickness, meibomian gland dropout and lid wiper epitheliopathy(p > 0.05). Meanwhile, in the demographic characteristics, statistically significant correlations were associated with skin property(r = 0.154, p = 0.001) and sleep duration(r=-0.124, p = 0.006), but not with age, sex, and the length of visual terminal use (p > 0.05). CONCLUSIONS: Lower TMH and shorter TBUT positively correlated with anterior location of the Marx's line, and were risk factors. Meanwhile, participants with oily skin and shorter sleep duration were more likely to exhibit anterior location of Marx's line.

Stepwise structural evolution toward robust carboranealkynyl-protected copper nanocluster catalysts for nitrate electroreduction.

Atomically precise metal nanoclusters (NCs) are emerging as idealized model catalysts for imprecise metal nanoparticles to unveil their structure-activity relationship. However, the directional synthesis of robust metal NCs with accessible catalytic active sites remains a great challenge. In this work, we achieved bulky carboranealkynyl-protected copper NCs, the monomer Cu13·3PF6 and nido-carboranealkynyl bridged dimer Cu26·4PF6, with fair stability as well as accessible open metal sites step by step through external ligand shell modification and metal-core evolution. Both Cu13·3PF6 and Cu26·4PF6 demonstrate remarkable catalytic activity and selectivity in electrocatalytic nitrate (NO3-) reduction to NH3 reaction, with the dimer Cu26·4PF6 displaying superior performance. The mechanism of this catalytic reaction was elucidated through theoretical computations in conjunction with in situ FTIR spectra. This study not only provides strategies for accessing desired copper NC catalysts but also establishes a platform to uncover the structure-activity relationship of copper NCs.

Current status of high-risk HPV infection and correlation with multiple infections in cervical lesions in Western Guangzhou.

Objective: This study aims to investigate the current status of multiple HPV infection and its association with cervical lesions in the western region of Guangzhou. Methods: A retrospective analysis of clinical data from cervical cancer screening patients was conducted. The patients were grouped based on HPV genotypes and cervical pathology results to explore the prevalence of high-risk HPV infection and its relationship with cervical lesions in the western region of Guangzhou. The study also analyzed the relationship between high-risk HPV infection and cervical lesions among different age groups. Results: A total of 13,060 patients were included in the study, with an overall infection rate of 18.46% (2,411/13,060). Among them, the infection rate of HPV genotype 16 was 14.14% (341/2,411), HPV genotype 18 was 5.23% (126/2,411), and other 12 high-risk HPV genotypes accounted for 71.96% (1,735/2,411). When comparing the incidence of HSIL+ (high-grade squamous intraepithelial lesion or worse) among different HPV genotypes, the results showed that the HPV 16 infection group (47.50%) had a higher incidence than the HPV 18 infection group (25.40%) and the other 12 high-risk HPV genotypes group (15.97%; P < 0.05). In the multiple infection groups, the pathogenicity rates were 63.64% (7/11) for the 16+18 HPV infection group, 42.97% (55/128) for the 16+other 12 high-risk HPV genotypes infection group, 26.79% (15/56) for the 18+other 12 high-risk HPV genotypes infection group, and 57.14% (8/14) for the 16+18+other 12 high-risk HPV genotypes infection group. These rates were significantly different compared to the single infection group (P <0.01). Although there was no statistically significant difference in the incidence of cervical cancer between the HPV 16 infection group and the HPV 18 infection group, both groups had a higher incidence compared to the group with other 12 high-risk HPV genotypes infection (P < 0.05). Further analysis suggests that the severity of cervical lesions is not associated with the number of high-risk HPV infections, i.e., the severity of cervical lesions is unrelated to multiple HPV infections but is instead related to the pathogenicity of the HPV genotypes. The infection rate and multiple HPV infection rate of women under 35 years old were higher than those of women aged 35 and above (20% vs. 17.1%; 2% vs. 1.3%; P < 0.05). Moreover, the pathogenicity rate of HSIL+ among high-risk HPV infection increased with age. Conclusions: In the western region of Guangzhou, the overall infection rate of high-risk HPV is 18.46%. The severity of cervical lesions is unrelated to multiple HPV infections. The fundamental reason is the distinct pathogenicity of different HPV genotypes. The HSIL+ pathogenicity rates, from high to low, are in sequence for HPV 16, HPV 18, and the other 12 HPV types.

Metabolite components and nutritional composition of the endosperm in seven species from Gleditsia.

As an important agricultural product, the endosperm portion of Gleditsia sinensis seeds, called "zào jiǎo mǐ" (ZJM) in Chinese, has gradually gained popularity and has been accepted by the public. However, there is limited information on the nutritional value and metabolic components of endosperm among Gleditsia. This study compared the endosperm composition among seven species. The types of metabolites, content of nutrients and amino acids were determined. A total of 4495 types of metabolites were detected. Galactose metabolism (gmx00052) was enriched in all combinations compared with G. sinensis. The polysaccharides content ranged from 51.49 to 80.37 g/100 g. Based on considerations of growth rate, seed yield, amino acid content, and interspecific differences, G. fera could be an alternative planting option to G. sinensis. These results can provide a reference for growers in selecting Gleditsia varieties and provide insights into the industrial applications of Gleditsia endosperm products.

Prognostic Value of Left Atrial Volume and Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Patients with Coronary Artery Disease and Severe Left Ventricular Dysfunction Underwent CABG.

RATIONALE AND OBJECTIVES: This study aims to investigate whether the combination of Left atrial volume (LAV) and late gadolinium enhancement (LGE) is helpful in stratifying the risk in CABG patients with CAD with EF≤ 35%. MATERIALS AND METHODS: We conducted a retrospective analysis involving 205 CAD patients with EF≤ 35% who underwent CABG. All patients underwent gadolinium-enhanced CMR before surgery. The CMR images were analyzed for LAV, biventricular function, LGE, and left ventricular myocardial strain. Primary endpoint events included all-cause mortality, revascularization, re-hospitalization due to myocardial infarction or heart failure, and stroke after CABG. Multivariable Cox analysis was performed to identify independent risk factors for adverse outcomes. Kaplan-Meier curve analysis with the log-rank test was employed to evaluate survival estimates. RESULTS: A total of 55 patients reached the primary endpoints. Univariate Cox proportional hazard regression analysis showed that LAV index (LAVi), left ventricular EF (LVEF), right ventricular EF, LGE percent, and global longitudinal strain were significantly associated with the primary outcome (all P < 0.05). Multivariable analysis showed that LAVi (hazard ratio [HR] 1.05, [95% confidence interval (CI) 1.02-1.07], P < 0.001) and LGE percent (HR 1.10, [95% CI 1.06-1.15], P < 0.001) were independently associated with the primary outcome. Kaplan-Meier analysis indicated a significant increase in the risk of endpoint occurrence when patients exhibited LAVi≥ 51.0 mL/m2 and LGE≥ 11.6% (both P < 0.05). CONCLUSION: For CAD patients with LVEF≤ 35%, the combination of LAVi and LGE percent demonstrated good predictive value for adverse events after CABG. CMR is a helpful tool to risk-stratify patients with severe left ventricular dysfunction undergoing CABG.

Discovery of novel coumarin-based KRAS-G12C inhibitors from virtual screening and Rational structural optimization.

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.

Association of sleep traits with benign prostatic hyperplasia in middle-aged and elderly men: A prospective analysis in UK Biobank.

AIMS: The association of sleep traits (insomnia, sleep duration, chronotype, daytime sleepiness, and snoring) with benign prostatic hyperplasia (BPH) is unclear. This research aimed to examine the effects of sleep traits on BPH risk. METHODS: A total of 170 241 men aged 38 to 73 years from UK Biobank were included. An overall healthy sleep score was created based on five sleep traits. A Cox regression model was utilized to compute adjusted hazard ratios (HRs) and population attributable fractions (PAFs) with 95% confidence intervals (CIs) for BPH risk in relation to sleep traits. RESULTS: During a median of 12.0 years follow-up, 13 026 incident BPH cases occurred. We observed that sleep duration (7-8 h/d; HR 0.95; 95% CI 0.92-0.99), no frequent insomnia (HR 0.71; 95% CI 0.69-0.74), and no frequent daytime sleepiness (HR 0.86; 95% CI 0.79-0.93) were significantly related to reduced BPH risk. Each one-point increment of the healthy sleep score was related to a decreased BPH risk, with an adjusted HR of 0.90 (95% CI 0.89-0.92). The multivariable-adjusted HR in men adopting five versus zero to one low-risk sleep traits was 0.68 (95% CI 0.61-0.75) for BPH risk. Estimates of the PAF indicated that 9.1% (95% CI 5.8-12.5%) of BPH cases would be prevented if all individuals had adopted all five low-risk sleep traits, assuming causality. CONCLUSIONS: Our study indicates an association between a healthy sleep pattern and a lower risk of BPH, emphasizing the importance of adhering to such patterns for potentially reducing BPH risk. Geriatr Gerontol Int 2024; ••: ••-••.

Transfer learning for anatomical structure segmentation in otorhinolaryngology microsurgery.

BACKGROUND: Reducing the annotation burden is an active and meaningful area of artificial intelligence (AI) research. METHODS: Multiple datasets for the segmentation of two landmarks were constructed based on 41 257 labelled images and 6 different microsurgical scenarios. These datasets were trained using the multi-stage transfer learning (TL) methodology. RESULTS: The multi-stage TL enhanced segmentation performance over baseline (mIOU 0.6892 vs. 0.8869). Besides, Convolutional Neural Networks (CNNs) achieved a robust performance (mIOU 0.8917 vs. 0.8603) even when the training dataset size was reduced from 90% (30 078 images) to 10% (3342 images). When directly applying the weight from one certain surgical scenario to recognise the same target in images of other scenarios without training, CNNs still obtained an optimal mIOU of 0.6190 ± 0.0789. CONCLUSIONS: Model performance can be improved with TL in datasets with reduced size and increased complexity. It is feasible for data-based domain adaptation among different microsurgical fields.