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Mai Zhang,1 Yan Li,1,2 Chunli Han,3 Shiying Chu,1 Peng Yu,1 Wenbo Cheng1,2 1Mass Spectrometry Application Center, Tianjin Guoke Medical Technology Development Co., Ltd, Tianjin, People’s Republic of China; 2Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences (CAS), Suzhou, People’s Republic of China; 3Mass Spectrometry Application Center, Shandong CAS Intelligent Manufacturing Medical Device Technology Co., Ltd, Zaozhuang, People’s Republic of ChinaCorrespondence: Wenbo Cheng, Email chengwb@sibet.ac.cnBackground: Inhibition of amyloid β protein fragment (Aβ) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer’s disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes.Materials and Methods: The interaction between EGCG and Aβ 42 was simulated by molecular docking, and green tea-conjugated gold nanoparticles (GT-Au NPs) and EGCG-Au NPs were synthesized using EGCG-enriched green tea and EGCG solutions, respectively. Surface active molecules of the particles were identified and analyzed using various liquid chromatography-tandem triple quadrupole mass spectrometry methods. ThT fluorescence assay, circular dichroism, and TEM were used to investigate the effect of synthesized particles on the inhibition of Aβ 42 aggregation.Results: EGCG as well as apigenin, quercetin, baicalin, and glutathione were identified as capping ligands stabilized on the surface of GT-Au NPs. They more or less inhibited Aβ 42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to Aβ 42 through hydrogen bonding, hydrophobic interactions, etc. resulting in 39.86% and 88.50% inhibition of aggregation and disaggregation effects, respectively. EGCG-Au NPs were not as effective as free EGCG, whereas multiple thiols and polyphenols in green tea accelerated and optimized heavy metal detoxification. The synthesized GT-Au NPs conferred the efficacy of diverse ligands to the particles, with inhibition of aggregation and disaggregation effects of 54.69% and 88.75%, respectively, while increasing the yield, enhancing water solubility, and decreasing cost.Conclusion: Biosynthesis of nanoparticles using green tea is a promising simple and economical drug-carrying approach to confer multiple pharmacophore molecules to Au NPs. This could be used to design new drug candidates to treat Alzheimer’s disease.Keywords: gold nanoparticles, green synthesis, (-)-epigallocatechin-3-gallate, liquid chromatography tandem triple quadrupole mass spectrometry, amyloid β protein, green tea

Fu Yu,1 Li Xia Zhao,2 Shangqi Chu3 1Department of Medical Oncology, Mingguang People’s Hospital of Anhui Province in China, Chuzhou, 239400, People’s Republic of China; 2Department of Radiation Oncology, Jieshou People’s Hospital of Anhui Province in China, Fuyang, 236500, People’s Republic of China; 3Department of Medical Oncology, Nantong Haimen District People’s Hospital, Nantong, Jiangsu Province, 226100, People’s Republic of ChinaCorrespondence: Shangqi Chu, Department of Medical Oncology, Nantong Haimen District People’s Hospital, Nantong, Jiangsu Province, 226100, People’s Republic of China, Tel/Fax +86-513-82263620, Email xingyun369302666@163.comBackground: This study aims to investigate the clinicopathological significance and prognostic value of Trichohyalin (TCHH) in gastric cancer patients through bioinformatics analysis.Materials and Methods: Data on TCHH expression and clinicopathological information were sourced from The Cancer Genome Atlas (TCGA). The Wilcoxon signed-rank test was used for evaluating the correlation between TCHH mRNA expression levels and clinicopathological features. The predictive significance of TCHH mRNA expression for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in patients with gastric cancer was assessed using Cox regression models. Furthermore, measures of immune cell infiltration in gastric cancer were made, and studies of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were also carried out to investigate the possible roles of TCHH in patients with gastric cancer.Results: Compared to normal tissues, gastric cancer had a considerably higher expression of TCHH mRNA (P < 0.05). Wilcoxon analysis revealed a significant association between TCHH mRNA expression and the pathologic M stage (P = 0.017). High TPMT mRNA levels were also correlated with worse OS, DFS, and PFI in gastric cancer patients (both P < 0.05). TCHH showed significant negative correlations with the levels of NK CD56dim infiltration (r = − 0.157, p = 0.002), Th17 cells infiltration (r = − 0.235, P < 0.001), and Th2 infiltration (r = − 0.195, P < 0.001). Furthermore, enrichment analysis indicated potential involvement in intermediate filament cytoskeleton organization, DNA methylation in gamete generation, cell-cell recognition, and G protein-coupled peptide receptor (GPCRs) activity.Conclusion: The level of TCHH mRNA may serve as a novel prognostic biomarker for gastric cancer patients.Keywords: gastric cancer, TCHH, biomarker, prognosis, bioinformatics

Weibing Xu,1 Yuxin Di,1 Shengjing Chu,1 Zixuan Wang,1 Haitao Long,1 Lumei Pu,1 Runtian Ma,1 Yanwei Wang2 1College of Science, Gansu Agricultural University, Lanzhou, 730000, People’s Republic of China; 2Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Astana, 010000, KazakhstanCorrespondence: Weibing Xu, College of Science, Gansu Agricultural University, No. 1 Yingmen Village, Anning District, Lanzhou, 730000, People’s Republic of China, Tel/Fax +86 931 7631212, Email xuwb@gsau.edu.cnBackground: Combination therapy employing multiple drugs has been shown to enhance the efficacy of cancer treatment. Chlorambucil (Chl) and 6-mercaptopurine (6MP) are the first-line medicines for chronic lymphocytic leukemia and ovarian cancer. However, both were limited by their short half-life of disintegration, unsatisfactory water solubility, and adverse reactions.Methods: In this work, the drug Chl and 6MP were introduced into the polymerized N-(2-hydroxypropyl) methacrylamide (polyHPMA) by pH and glutathione responsive linker to construct the polymer nanodrug delivery system for effective co-delivery.Results: The drug load capacities, release, morphology, and cytotoxicity of the pro-drug were systematic. The two drugs showed satisfactory synergism with a combination index of 0.81, and a better ability to induce apoptosis. In and ex vivo fluorescence imaging showed a rapid systemic distribution of the conjugate within mice, majorly metabolized by liver and kidneys and eliminated after 24 hr. No significant pathological damage was observed in the major organs. This polymeric prodrug system holds promise for improved therapeutic efficiency and reduced side effects through the synergistic delivery of various chemotherapeutics.Conclusion: The introduction of HPMA as a carrier not only enhanced the solubility and biocompatibilities of Chl and 6 MP but also improved their drug effect. This strategy might be a promising alternative for constructing multi-drug-release system. Keywords: polymer prodrug, co-delivery, chlorambucil, mercaptopurine, fluorescence images, cancer treatment

Si Dung Chu,1,2 Minh Thi Tran2 1Haiphong - Vinhbao International General Hospital, Hai Phong City, Vietnam; 2Internal Medicine Department, Vietnam University of Traditional Medicine, Hanoi Capital, VietnamCorrespondence: Si Dung Chu, Department of Internal Medicine, Vietnam University of Traditional Medicine, Hanoi, Vietnam, Tel +84 906086168, Email sichu.bvbachmai@gmail.comObjective: Study on effect of risk factors on over-anticoagulation in patients taking anticoagulant drugs with VKAs (vitamin K antagonists).Methods: Cross-sectional descriptive, prospective research. Study on 79 patients taking anticoagulant drugs with VKAs who had an INR (International Normalized Ratio) index of more than indicated anticoagulation dose with VKAs therapy.Results: A total of 79 patients, mean age 65.65 ± 12.17 years [33:85], the elderly group is common (73.4%). Patients had hemorrhage disorders account for 22.8%. The INR index had an average value was 5.88 ± 3.0 [3.02– 23.95]; The INR> 5 level group is a higher risk of bleeding than the INR ≤ 5 level group, it’s the statistical significance (p < 0.001). The risk factors such as drugs to treat dyslipidemia, hyperthyroid, amiodarone, beta blocker, prednisone, NSAIDs (Non-steroidal anti-inflammatory), BMI (Body Mass Index), smoke and alcohol that the risk factors of increasing of bleeding when receiving anticoagulants but it’s not statistically significant yet (OR > 1, p > 0.05); These patients using coenzyme Q10 and green vegetable nutrition such as cruciferous vegetables (Brassicaceae, Asteraceae) are quite common (31.6% and 35.4%), its effect on coagulation with vitamin K and cause of the increased in risk of bleeding was statistical significantly with OR = 5.28 (CI: 1.72– 16.17, p < 0.01), and OR = 2.99 (CI: 1.01– 8.80, p < 0.05) respectively.Conclusion: Most patients in over-anticoagulation were the elderly group. Patients had hemorrhage disorders account for 22.8%. The INR> 5 level group was a higher risk of bleeding than the INR ≤ 5 level group with statistical significance. Patients using Coenzyme Q10 and green vegetable nutrition such as cruciferous vegetables (Brassicaceae, Asteraceae) are quite common, its effect on coagulation and cause of the increased risk of bleeding complication with statistical significance.Keywords: risk factors, bleeding, VKAs overdose, INR

Recent years have witnessed remarkable progress in enhancing the supercontinuum (SC) generation in highly nonlinear photonic integrated waveguides. In this study, we conduct a comprehensive investigation into supercontinuum (SC) generation in high-index doped silica glass integrated waveguides. We explore a variety of femtosecond pumping wavelengths and input polarization states, demonstrating octave-spanning SC bandwidth from visible to mid-infrared wavelengths.

Alkali-activated materials (AAMs) are promising alternatives to ordinary Portland cement (OPC), but standardized mix design approaches are limited. This study introduces a machine learning-based framework for inverse mix design of AAMs, predicting optimal mixes based on target properties and sustainability. The model considers eight key factors, including precursor reactivity, activator properties, and liquid-to-binder ratio. It operates in four steps: (i) constructing forward prediction models, (ii) generating new mix designs, (iii) evaluating workability and strength, and (iv) filtering for performance and sustainability. Experiments validated the model, targeting fluidity >100% and compressive strengths of 40 MPa (A40) and 50 MPa (A50). The A40 and A50 mixes achieved fluidities of 147.7% and 170.0%, and 28-day compressive strengths of 41.5 and 57.5 MPa. Both had lower environmental impacts (GWP, AP, and EP) compared to OPC-based mortars. This framework enhances AAM design efficiency and sustainability for broader applications. [ABSTRACT FROM AUTHOR]

Although many aspects of blood production are well understood, the spatial organization of myeloid differentiation in the bone marrow remains unknown. Here we use imaging to track granulocyte/macrophage progenitor (GMP) behaviour in mice during emergency and leukaemic myelopoiesis. In the steady state, we find individual GMPs scattered throughout the bone marrow. During regeneration, we observe expanding GMP patches forming defined GMP clusters, which, in turn, locally differentiate into granulocytes. The timed release of important bone marrow niche signals (SCF, IL-1β, G-CSF, TGFβ and CXCL4) and activation of an inducible Irf8 and β-catenin progenitor self-renewal network control the transient formation of regenerating GMP clusters. In leukaemia, we show that GMP clusters are constantly produced owing to persistent activation of the self-renewal network and a lack of termination cytokines that normally restore haematopoietic stem-cell quiescence. Our results uncover a previously unrecognized dynamic behaviour of GMPs in situ, which tunes emergency myelopoiesis and is hijacked in leukaemia.

The US DOE-funded National Risk Assessment Partnership (NRAP) has developed an integrated assessment model (NRAP-IAM-CS) that can be used to simulate carbon dioxide (CO2) injection, migration, and associated impacts at a geologic carbon storage site. The model, NRAP-IAM-CS, incorporates a system-modeling-based approach while taking into account the full subsurface system from the storage reservoir to groundwater aquifers and the atmosphere. The approach utilizes reduced order models (ROMs) that allow fast computations of entire system performance even for periods of hundreds to thousands of years. The ROMs are run in Monte Carlo mode allowing estimation of uncertainties of the entire system without requiring long computational times. The NRAP-IAM-CS incorporates ROMs that realistically represent several key processes and properties of storage reservoirs, wells, seals, and groundwater aquifers. Results from the NRAP-IAM-CS model are used to quantify risk profiles for selected parameter distributions of reservoir properties, seal properties, numbers of wells, well properties, thief zones, and groundwater aquifer properties. A series of examples is used to illustrate how the risk under different storage conditions evolves over time, both during injection, in the near-term post injection period, and over the long term. It is also shown how results from NRAP-IAM-CS can be used to investigate the importance of different parameters on risk of leakage and risk of groundwater contamination under different storage conditions.

Lanthanide-based upconverting nanoparticles exhibit significant promise for solar energy generation, biological imaging, and security technologies but have not seen widespread adoption due to the prohibitively low efficiencies of current materials. Weak transition dipole moments between 4f orbitals hinder both photon absorption and emission. Here, we introduce a novel way to increase the radiative transition rates in Yb,Er-based upconverting nanoparticles based on local symmetry distortion. Beginning from a host matrix of the well-studied hexagonal (β)-phase NaYF4, we incrementally remove Y3+ ions and cosubstitute for them a 1:1 mixture of Gd3+ and Lu3+. These two ions act to expand and contract the lattice, respectively, inducing local-level distortion while maintaining the average host structure. We synthesize a range of β-NaY0.8-2xGdxLuxF4:Yb0.18Er0.02 nanoparticles and experimentally confirm that particle size, phase, global structure, and Yb3+ and Er3+ concentrations remain constant as x is varied. Upconversion quantum yield is probed as the degree of cosubstitution is varied from x = 0 to x = 0.24. We achieve a maximum quantum yield value of 0.074% under 63 W/cm2 of excitation power density, representing a 1.6× enhancement over the unmodified particles and the highest measured value for near-infrared-to-visible upconversion in sub-25 nm unshelled nanoparticles. We also investigate upconversion emission at the single-particle level and report record improvements in emission intensity for sub-50 nm particles. Radiative rate enhancements are confirmed by measuring excited-state lifetimes. The approach described herein can be used in combination with more established methods of efficiency improvement, such as adding passivating shells or coupling to plasmonic nanoattenas, to further boost the upconversion quantum yield.

Jie Xia,1– 4,* Lina Sun,5,* Suqin Xu,1– 4 Qiu Xiang,1– 4 Jianping Zhao,1– 4 Weining Xiong,1– 4 Yongjian Xu,1– 4 Shuyuan Chu1– 4,6 1Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 2Wuhan Clinical Medical Research Center for Chronic Airway Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 3Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 4Key Site of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 6Laboratory of Respiratory Disease, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuyuan Chu; Jie XiaDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of ChinaTel +8613978345180; +8627-83665520Email emilyyuanchu@163.com; xiajhzu1215@126.comPurpose: Patients with chronic obstructive pulmonary disease (COPD) would have a poor prognosis if they were not continuously managed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. We aim to develop a model to classify whether COPD patients have been continuously managed according to GOLD in the previous year.Methods: The Managed group were COPD patients from a prospective cohort from November 2017 to November 2019, who have been continuously managed according to GOLD for 1 year. The Control group were COPD patients who were not continuously managed according to GOLD. They were from a retrospective cohort from October 2016 to October 2017 in the same hospitals as the Managed group. A synthetic minority over-sampling technique (SMOTE) algorithm was used to up-sample the Managed group in a training dataset. Features for classification were selected using a support vector machine recursive feature elimination (SVM-RFE) algorithm. The classification model was developed using LibSVM, and its performance was assessed on the testing dataset.Results: The final analysis included 15 subjects in the Managed group and 191 in the Control group. SVM-RFE selects nine features including smoking history, post-bronchodilator (post-)FVC before management, and those after 1-year follow-up (BMI, moderate and severe AECOPD frequency in previous 12 months, mMRC score, post-FEV1, post-FEV1%pred, post-FVC, and post-FEV1/FVC). For our model, positive predictive value is 66.7%, F1 score is 0.978, and AUC is 0.987.Conclusion: SVM classifier combined with SVM-REF feature selection algorithm could achieve good classification between COPD patients who are or are not continuously managed. This model could be applied in clinical practice to help doctors make decisions and enhance COPD patients’ compliance with standard treatment.Keywords: COPD, GOLD, continuous management, support vector machine