Responses of physiological, microbiome and lipid metabolism to lignocellulose wastes in gut of yellow mealworm (Tenebrio molitor).

There is limited research on physiological and degradation mechanisms of yellow mealworm, a novel organic waste converter, in processing lignocellulosic wastes. This study has selected two types of lignocellulosic wastes, distillers' grains (DG) and maize straw (MS), to feed yellow mealworms. This study investigated the effects of lignocellulosic wastes on the growth, antioxidant system, microbiome, and lipidome of yellow mealworms. The relative growth of lignocellulosic waste group was not significantly different from wheat bran. The antioxidant level was elevated in DG. MS was significantly enriched in cellulose-degrading bacteria in the gut and was accompanied by disturbances in lipid metabolism. The correlation coefficients were used to construct a network connecting diet, microbiota, and lipids. The correlation analysis indicated that two sphingolipids, hexylglyceramide and dihydroglyceramide, were strongly and positively linked with the dominating species. This study provides comprehensive information on physiological and mechanism of mealworms in process of treating lignocellulosic waste.

Automated osteoporosis classification and T-score prediction using hip radiographs via deep learning algorithm.

Background: Despite being the gold standard for diagnosing osteoporosis, dual-energy X-ray absorptiometry (DXA) is an underutilized screening tool for osteoporosis. Objectives: This study proposed and validated a controllable feature layer of a convolutional neural network (CNN) model with a preprocessing image algorithm to classify osteoporosis and predict T-score on the proximal hip region via simple hip radiographs. Design: This was a single-center, retrospective study. Methods: An image dataset of 3460 unilateral hip images from 1730 patients (age ⩾50 years) was retrospectively collected with matched DXA assessment for T-score for the targeted proximal hip regions to train (2473 unilateral hip images from 1430 patients) and test (497 unilateral hip images from 300 patients) the proposed CNN model. All images were processed with a fully automated CNN model, X1AI-Osteo. Results: The proposed screening tool illustrated a better performance (sensitivity: 97.2%; specificity: 95.6%; positive predictive value: 95.7%; negative predictive value: 97.1%; area under the curve: 0.96) than the open-sourced CNN models in predicting osteoporosis. Moreover, when combining variables, including age, body mass index, and sex as features in the training metric, there was high consistency in the T-score on the targeted hip regions between the proposed CNN model and the DXA (r = 0.996, p < 0.001). Conclusion: The proposed CNN model may identify osteoporosis and predict T-scores on the targeted hip regions from simple hip radiographs with high accuracy, highlighting the future application for population-based opportunistic osteoporosis screening with low cost and high adaptability for a broader population at risk. Trial registration: TMU-JIRB N201909036.

Reassessing clinical presentations of emamectin benzoate poisoning: A comprehensive study.

BACKGROUND: The mechanism of emamectin benzoate (EMB-a macrocyclic lactone insecticide like abamectin) action involves the disruption of glutamate-gated chloride channels and GABA receptors in insects, leading to paralysis and death. EMB overdose can breach the blood-brain barrier, resulting in severe poisoning and altered consciousness. AIM: Review EMB poisoning presentations in patients and reevaluate clinical manifestations. MATERIALS AND METHODS: This retrospective study reviewed (August 31, 2008-August 31, 2023) medical university hospital records. We analyzed symptoms, patient characteristics, vital signs, Glasgow Coma Scale scores, laboratory findings, and outcomes. RESULTS: Ten patients (males: 6, females: 4, median age = 64.5 years) experienced EMB poisoning. Common symptoms included sore throat, gastrointestinal distress, dyspnea, and altered consciousness; two patients showed laryngeal corrosive injuries. Management involved activated charcoal administration, gastric lavage, and intensive care unit admission. DISCUSSION: Sore throat and corrosive injuries were distinctive presentations of EMB poisoning, warranting vigilance. Potential mechanisms of corrosive injury include skin and eye irritation effects of EMB, the solvents of which might exert corrosive action. CONCLUSION: EMB poisoning manifests as diverse symptoms, including sore throat, gastrointestinal symptoms, central nervous system depression, and potential aspiration pneumonia. Recognizing and promptly managing EMB poisoning are crucial for enhancing patient outcomes and minimizing complications.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Design of robotic arm for the porcelain bushing in substation.

With the development and the application popularization of artificial intelligence robot technology and 5G technology, a robotic arm is designed and developed for rinsing porcelain bushing in high voltage substation in this paper. Firstly, the components and implementation of robotic arm are presented, subsequently, a circular cleaning structure with a 120-degree split is proposed to rinse the porcelain bushing. Secondly, a two-stage simple and effective method to realize automatic orientation is proposed utilizing photoelectric switches. Moreover, a prototype of robotic arm with control system is developed based on the regime switching function, and the result of edge computing is transmitted by 5G technology. Finally, feasibility and effectiveness of the robotic arm are verified in the Nanjing power grid. The case study manifests that the robotic arm developed by the proposed method in the paper can achieve efficient rinsing and all the corresponding information can be transmitted preciously. The proposed method lays a foundation for wide application of cleaning robot in high voltage substation.

Combined untargeted metabolomics and network pharmacology approaches to reveal the therapeutic role of withanolide B in psoriasis.

Psoriasis is a refractory inflammatory skin disorder in which keratinocyte hyperproliferation is a crucial pathogenic factor. Up to now, it is commonly acknowledged that psoriasis has a tight connection with metabolic disorders. Withanolides from Datura metel L. (DML) have been proved to possess anti-inflammatory and anti-proliferative properties in multiple diseases including psoriasis. Withanolide B (WB) is one of the abundant molecular components in DML. However, existing experimental studies regarding the potential effects and mechanisms of WB on psoriasis still remain lacking. Present study aimed to integrate network pharmacology and untargeted metabolomics strategies to investigate the therapeutic effects and mechanisms of WB on metabolic disorders in psoriasis. In our study, we observed that WB might effectively improve the symptoms of psoriasis and alleviate the epidermal hyperplasia in imiquimod (IMQ)-induced psoriasis-like mice. Both network pharmacology and untargeted metabolomics results suggested that arachidonic acid metabolism and arginine and proline metabolism pathways were linked to the treatment of psoriasis with WB. Meanwhile, we also found that WB may affect the expression of regulated enzymes 5-lipoxygenase (5-LOX), 12-LOX, ornithine decarboxylase 1 (ODC1) and arginase 1 (ARG1) in the arachidonic acid metabolism and arginine and proline metabolism pathways. In summary, this paper showed the potential metabolic mechanisms of WB against psoriasis and suggested that WB would have greater potential in psoriasis treatment.

Evaluating the developmental potential of 2.1PN-derived embryos and associated chromosomal analysis.

PURPOSE: Zygotes with 2.1 pronuclei (2.1PN) present with two normal-sized pronuclei, and an additional smaller pronucleus, that is approximately smaller than two thirds the size of a normal pronucleus. It remains unclear whether the additional pronucleus causes embryonic chromosome abnormalities. In the majority of cases, in vitro fertilization (IVF) clinics discarded 2.1PN zygotes. Thus, the present study aimed to evaluate the developmental potential and value of 2.1PN zygotes. METHODS: 2.1PN-derived embryos from 164 patients who underwent IVF or intracytoplasmic sperm injection (ICSI) treatment between January 2021 and December 2022 were included in the present study. All embryos were monitored using a time-lapse system, and blastocyst formation was used to assess 2.1PN-derived embryo developmental potential. The blastocyst formation was quantified using generalized estimating equations, and chromosome euploidy was analyzed using next-generation sequencing (NGS). In addition, the potential association between age and occurrence of 2.1PN zygotes was determined. RESULTS: The present study demonstrated that numerous 2.1PN zygotes developed into blastocysts. Early cleavage patterns and embryo quality on Day 3 were the independent predictors for the blastocyst formation of 2.1PN-derived embryos. The 2.1PN zygotes displayed a comparable developmental potential compared to 2PN zygotes in advanced age patients (≥ 38). Moreover, there was a tendency that 2.1PN-derived blastocysts showed a similar euploidy rate compared to 2PN-derived blastocysts. CONCLUSION: Clinicians should consider using 2.1PN-derived euploid embryos for transfer after preimplantation genetic testing in the absence of available 2PN embryo cycles. 2.1PN-derived embryos could be a candidate, particularly beneficial for patients at advanced age.

Chemical inertness conversion of carbon fraction in coal gangue via N-doping for efficient benzo(a)pyrene degradation.

Efficient degradation of organic pollutants in complex media via advanced oxidation processes (AOPs) is still critical and challenging. Herein, nitrogen (N)-doped coal gangue (CG) catalysts (N-CG) with economic competitiveness and environmental friendliness were successfully synthesized to activate peroxymonosulfate (PMS), exhibiting ultrafast degradation performance toward benzo(a)pyrene (BaP) with 100.00 % and 93.21 % in contaminated solution and soil under optimized condition, respectively. In addition, 0.4 N-CG possessed excellent reusability toward BaP degradation with over 80.00 % after five cycles. However, BaP removal efficiency was significantly affected by some co-existing anions (HCO3- and SO42-) and humic acid (HA) in solution and soil, as well as inhibited under alkaline conditions, especially pH ≥ 9. According to the characterizations, N-doping could promote the generation of pyridinic N and graphitic N in N-CG via high-temperature calcination, which was conducive to produce hydroxyl radical (•OH), sulfate radical (SO4•-), superoxide radical (•O2-) and single oxygen (1O2). In 0.4 N-CG/PMS system, 1O2 and •O2- were proved to be the predominant reactive oxygen species (ROSs) in BaP degradation, as well as •OH and SO4•- made certain contributions. To sum up, this work provided a promising strategy for synthesis of CG-based catalysts by chemical inertness conversion of carbon fracture via N-doping for PMS activation and opened a novel perspective for environmental remediation of hydrophobic and hydrophilic contaminants pollution.

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone-Related Diseases: Intercellular Communication Messengers and Therapeutic Engineering Protagonists.

Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs but with drawbacks such as lower yield, reduced biological activities, off-target effects, and shorter half-lives. Improving strategies utilizing biotechniques to pretreat MSCs and enhance the properties of released EVs, as well as modifying MSC-EVs to enhance targeting abilities and achieve controlled release, shows potential for overcoming application limitations and enhancing therapeutic effects in treating bone-related diseases. This review focuses on recent advances in functionalizing MSC-EVs to treat bone-related diseases. Firstly, we underscore the significance of MSC-EVs in facilitating crosstalk between cells within the skeletal environment. Secondly, we highlight strategies of functional-modified EVs for treating bone-related diseases. We explore the pretreatment of stem cells using various biotechniques to enhance the properties of resulting EVs, as well as diverse approaches to modify MSC-EVs for targeted delivery and controlled release. Finally, we address the challenges and opportunities for further research on MSC-EVs in bone-related diseases.

Deciphering microglial activation and neuronal apoptosis post­traumatic brain injury: The role of TYROBP in inflammation regulation networks.

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro­arrays, high­throughput RNA sequencing and single­cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase­binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF­α), vascular endothelial growth factor and transforming growth factor ß via the NF­κB pathway. Cells co­culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non­contact mechanisms. Activated microglia secrete cytokines, including TNF­α, CXCL­8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.

Time-dependent CT score-based model for identifying severe/critical COVID-19 at a fever clinic after the emergence of Omicron variant.

Rationale and objectives: The computed tomography (CT) score has been used to evaluate the severity of COVID-19 during the pandemic; however, most studies have overlooked the impact of infection duration on the CT score. This study aimed to determine the optimal cutoff CT score value for identifying severe/critical COVID-19 during different stages of infection and to construct corresponding predictive models using radiological characteristics and clinical factors. Materials and methods: This retrospective study collected consecutive baseline chest CT images of confirmed COVID-19 patients from a fever clinic at a tertiary referral hospital from November 28, 2022, to January 8, 2023. Cohorts were divided into three subcohorts according to the time interval from symptom onset to CT examination at the hospital: early phase (0-3 days), intermediate phase (4-7 days), and late phase (8-14 days). The binary endpoints were mild/moderate and severe/critical infection. The CT scores and qualitative CT features were manually evaluated. A logistic regression analysis was performed on the CT score as determined by a visual assessment to predict severe/critical infection. Receiver operating characteristic analysis was performed and the area under the curve (AUC) was calculated. The optimal cutoff value was determined by maximizing the Youden index in each subcohort. A radiology score and integrated models were then constructed by combining the qualitative CT features and clinical features, respectively, using multivariate logistic regression with stepwise elimination. Results: A total of 962 patients (aged, 61.7 ± 19.6 years; 490 men) were included; 179 (18.6%) were classified as severe/critical COVID-19, while 344 (35.8%) had a typical Radiological Society of North America (RSNA) COVID-19 appearance. The AUCs of the CT score models reached 0.91 (95% confidence interval (CI) 0.88-0.94), 0.82 (95% CI 0.76-0.87), and 0.83 (95% CI 0.77-0.89) during the early, intermediate, and late phases, respectively. The best cutoff values of the CT scores during each phase were 1.5, 4.5, and 5.5. The predictive accuracies associated with the time-dependent cutoff values reached 88% (vs.78%), 73% (vs. 63%), and 87% (vs. 57%), which were greater than those associated with universal cutoff value (all P < 0.001). The radiology score models reached AUCs of 0.96 (95% CI 0.94-0.98), 0.90 (95% CI 0.87-0.94), and 0.89 (95% CI 0.84-0.94) during the early, intermediate, and late phases, respectively. The integrated models including demographic and clinical risk factors greatly enhanced the AUC during the intermediate and late phases compared with the values obtained with the radiology score models; however, an improvement in accuracy was not observed. Conclusion: The time interval between symptom onset and CT examination should be tracked to determine the cutoff value for the CT score for identifying severe/critical COVID-19. The radiology score combining qualitative CT features and the CT score complements clinical factors for identifying severe/critical COVID-19 patients and facilitates timely hierarchical diagnoses and treatment.

Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Predicting Invasiveness of Lung Adenocarcinoma at Chest CT with Deep Learning Ternary Classification Models.

Background Preoperative discrimination of preinvasive, minimally invasive, and invasive adenocarcinoma at CT informs clinical management decisions but may be challenging for classifying pure ground-glass nodules (pGGNs). Deep learning (DL) may improve ternary classification. Purpose To determine whether a strategy that includes an adjudication approach can enhance the performance of DL ternary classification models in predicting the invasiveness of adenocarcinoma at chest CT and maintain performance in classifying pGGNs. Materials and Methods In this retrospective study, six ternary models for classifying preinvasive, minimally invasive, and invasive adenocarcinoma were developed using a multicenter data set of lung nodules. The DL-based models were progressively modified through framework optimization, joint learning, and an adjudication strategy (simulating a multireader approach to resolving discordant nodule classifications), integrating two binary classification models with a ternary classification model to resolve discordant classifications sequentially. The six ternary models were then tested on an external data set of pGGNs imaged between December 2019 and January 2021. Diagnostic performance including accuracy, specificity, and sensitivity was assessed. The χ2 test was used to compare model performance in different subgroups stratified by clinical confounders. Results A total of 4929 nodules from 4483 patients (mean age, 50.1 years ± 9.5 [SD]; 2806 female) were divided into training (n = 3384), validation (n = 579), and internal (n = 966) test sets. A total of 361 pGGNs from 281 patients (mean age, 55.2 years ± 11.1 [SD]; 186 female) formed the external test set. The proposed strategy improved DL model performance in external testing (P < .001). For classifying minimally invasive adenocarcinoma, the accuracy was 85% and 79%, sensitivity was 75% and 63%, and specificity was 89% and 85% for the model with adjudication (model 6) and the model without (model 3), respectively. Model 6 showed a relatively narrow range (maximum minus minimum) across diagnostic indexes (accuracy, 1.7%; sensitivity, 7.3%; specificity, 0.9%) compared with the other models (accuracy, 0.6%-10.8%; sensitivity, 14%-39.1%; specificity, 5.5%-17.9%). Conclusion Combining framework optimization, joint learning, and an adjudication approach improved DL classification of adenocarcinoma invasiveness at chest CT. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Sohn and Fields in this issue.

Consistent efficacy outcomes between phase 2 and phase 3 trials in Crohn's disease or ulcerative colitis in adults: a meta-analysis.

INTRODUCTION: The approval of novel biologic agents and small molecules for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) is dependent on phase 3 randomized controlled trials (RCTs). However, these trials sometimes fail to achieve the expected efficacy outcomes observed in phase 2 trials. METHODS: We conducted a systematic review of RCTs that evaluated biologic agents and small molecules using paired regimens in both phase 2 and phase 3. We searched Medline, EMBASE, and Cochrane databases up until February 13, 2024. The revised Cochrane tool was utilized to assess the risk of bias. A generalized linear mixed-effects model (GLMM) was employed to estimate the odds ratios (ORs) for efficacy outcomes in phase 2 trials compared to phase 3. RESULTS: We identified a total of 23 trials with 10 paired regimens for CD and 30 trials with 11 paired regimens for UC. The GLMM analysis revealed that phase 2 CD trials had higher outcomes measured by the Crohn's Disease Activity Index (CDAI) by 9-13% without statistical significance: CDAI-150: OR, 1.12 (95% CI 0.83-1.51, p = 0.41); CDAI-100: OR, 1.09 (95% CI 0.88-1.35, p = 0.40); or CDAI-70: OR, 1.13 (95% CI 0.61-2.08, p = 0.66). For UC, two efficacy outcomes were estimated to be equally reported in phase 2/phase 3 pairs: clinical remission: OR, 1.00 (95% CI 0.83-1.20, p = 0.96); endoscopic improvement: OR, 0.98 (95% CI 0.83-1.15, p = 0.79). However, the rate of clinical response was underestimated in phase 2 by 19%: OR, 0.81 (95% CI 0.70-0.95, p = 0.03). The inclusion criterion for the type of Mayo score for UC had a significant interaction with the study phase to influence the difference in clinical response (p = 0.002). CONCLUSIONS: Our findings suggest that the main efficacy outcomes for CD and UC remain consistent between phase 2 and phase 3 trials, except for UC response rates. The efficacy data obtained from phase 2 trials can be considered reliable for the design of subsequent phase 3 trials. REGISTRATION: PROSPERO (CRD42023407947).

The Preparation of an Ultrafine Copper Powder by the Hydrogen Reduction of an Ultrafine Copper Oxide Powder and Reduction Kinetics.

Ultrafine copper powders were prepared by the air-jet milling of copper oxide (CuO) powders and a subsequent hydrogen (H2) reduction. After milling, the particle size and grain size of CuO powders decreased, while the specific surface area and structural microstrain increased, thereby improving the reaction activity. In a pure H2 atmosphere, the process of CuO reduction was conducted in one step, and followed a pseudo-first-order kinetics model. The smaller CuO powders after milling exhibited higher reduction rates and lower activation energies compared with those without milling. Based on the unreacted shrinking core model, the reduction of CuO powders via H2 was controlled by the interface reaction at the early stage, whereas the latter was limited by the diffusion of H2 through the solid product layer. Additionally, the scanning electron microscopy (SEM) indicated that copper powders after H2 reduction presented a spherical-like shape, and the sintering and agglomeration between particles occurred after 300 °C, which led to a moderate increase in particle size. The preparing parameters (at 400 °C for 180 min) were preferred to obtain ultrafine copper powders with an average particle size in the range of 5.43-6.72 µm and an oxygen content of less than 0.2 wt.%.

Effects of aspirin on colon cancer using quantitative proteomic analysis.

Background: Colon cancer is one of the most prevalent digestive cancers worldwide. Results of epidemiological, experimental, and clinical studies suggest that aspirin inhibits the development of colon cancer. This study aimed to systematically elucidate the molecular mechanisms by which aspirin prevents colon carcinogenesis. Methods: We determined the global protein expression profiles of colorectal cancer and aspirin-treated cells using quantitative proteomic analysis. We analyzed the proteomic results using bioinformatics (including differential proteins, protein annotation, Kyoto Encyclopedia of Genes and Genomes [KEGG] pathways, and protein-protein interaction [PPI] network). The viability of the colon cancer cell line and HT29 â€‹cells treated with aspirin was determined using the cell counting kit-8 assay. The differentially expressed proteins, such as p53 and cyclin-dependent kinase 1 (CDK1), were quantified using real-time polymerase chain reaction (PCR) and Western blotting. We measured cell cycle distribution and apoptosis in HT29 â€‹cells exposed to aspirin using fluorescence-activated cell sorting (FACS). Results: We found that 552 proteins were significantly dysregulated, of which 208 and 334 were upregulated and downregulated, respectively, in colon cancer cells exposed to 10 â€‹mmol/L of aspirin (95% confidence interval [CI]: -1.269 to -0.106, P â€‹< â€‹0.05). Further gene enrichment analysis revealed that cell cycle-related proteins, such as p53 and CDK1, were significantly differentially expressed. Proteomic analysis showed that after 24 â€‹h of aspirin exposure, the level of p53 increased by 2.52-fold and CDK1 was downregulated to half that of the controls in HT29 â€‹cells (95% CI: -0.619 to -0.364, P â€‹< â€‹0.05). Real-time PCR and Western blotting results showed that p53 was upregulated (95%CI: -3.088 to -1.912, P â€‹< â€‹0.001) and CDK1 was significantly downregulated after aspirin exposure in colon cancer cells (95% CI: 0.576 to 1.045, P â€‹< â€‹0.05). We observed that aspirin promoted G1/S cell cycle arrest in HT29 â€‹cells. We confirmed that aspirin induces apoptosis in human HT29 colon cancer cells in a concentration-dependent manner. Conclusions: These results indicate that aspirin induces G1 arrest and apoptosis in colorectal cancer cells via the p53-CDK1 pathway. Aspirin may be a promising drug candidate for colon cancer prevention.

Sulfonium-Stapled Peptides-Based Neoantigen Delivery System for Personalized Tumor Immunotherapy and Prevention.

Neoantigen peptides hold great potential as vaccine candidates for tumor immunotherapy. However, due to the limitation of antigen cellular uptake and cross-presentation, the progress with neoantigen peptide-based vaccines has obviously lagged in clinical trials. Here, a stapling peptide-based nano-vaccine is developed, comprising a self-assembly nanoparticle driven by the nucleic acid adjuvant-antigen conjugate. This nano-vaccine stimulates a strong tumor-specific T cell response by activating antigen presentation and toll-like receptor signaling pathways. By markedly improving the efficiency of antigen/adjuvant co-delivery to the draining lymph nodes, the nano-vaccine leads to 100% tumor prevention for up to 11 months and without tumor recurrence, heralding the generation of long-term anti-tumor memory. Moreover, the injection of nano-vaccine with signal neoantigen eliminates the established MC-38 tumor (a cell line of murine carcinoma of the colon without exogenous OVA protein expression) in 40% of the mice by inducing potent cytotoxic T lymphocyte infiltration in the tumor microenvironment without substantial systemic toxicity. These findings represent that stapling peptide-based nano-vaccine may serve as a facile, general, and safe strategy to stimulate a strong anti-tumor immune response for the neoantigen peptide-based personalized tumor immunotherapy.