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Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 765-780页

作者： Siqin He Lulu Wang Dongxu Wu Fan Tong huan zhao Hanmei Li Tao Gong Huile Gao Yang Zhou Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikou 570200China Key Laboratory of Drug-Targeting and Drug Delivery System West China School of PharmacySichuan UniversityChengdu 610041China Revvity Inc. WalthamMA 02451USA School of Food and Biological Engineering Chengdu UniversityChengdu 610106China

A major challenge facing photodynamic therapy(PDT) is that the activity of the immuneinduced infiltrating CD8^(+)T cells is subject to the regulatory T lymphocytes(Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment(TME), a supramolecular photodynamic nanoparticle(DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin(DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration(Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs.The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

关键词： Photodynamic therapy Immunosuppressive microenvironment Immunomodulator Dual-responsive Supramolecularassembly Checkpointblockade

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Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第3期36卷 306-321页

作者： Zhifei Li huan zhao Huihui Hu Haili Shang Yongjing Ren Wenhui Qiu Hao Su Huifang Lyu Xiaobing Chen Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer Hospital Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer Henan University of Traditional Chinese Medicine State Key Laboratory of Esophageal Cancer Prevention&Treatment Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education School of Pharmaceutical SciencesZhengzhou University The First Affiliated Hospital of Xinxiang Medical University Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer Hospital

Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2(HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

关键词： HER2 gastric cancer trastuzumab drug resistance

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Hydrogen storage thermodynamics and kinetics of as-cast Ce-Mg-Ni-based alloy

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Journal of Iron and Steel Research(International) 2024年第3期31卷 752-766页

作者： Yan Qi Xin Zhang Jun Li Dong-liang zhao Shi-hai Guo Yang-huan Zhang Department of Functional Material Research Central Iron and Steel Research InstituteBeijing 100081China China Rare Earth New Material(Weishan)Co..Ltd. Jining 277600ShandongChina Collaborative Innovation Center of Integrated Exploitation of Bayan Obo Multi-Metal Resources Inner Mongolia University of Science and TechnologyBaotou 014010Inner MongoliaChina

The reaction kinetics of alloys based on magnesium are known to be greatly improved by the partial substitution of Mg with rare earths and transition metals,particularly Ni.The enhanced superficial hydrogen dissociation rate,the weakened Mg-H bond and the lower activation energy following element replacement are thought to be related to the better performance.The experimental alloys Ce5Mg_(95-x)Ni_(x)(x=5,10,15)were smelted by the vacuum induction melting.The phase transformation and structural evolution of experimental alloys before and after reaction with hydrogen were char-acterized by X-ray diffraction,scanning electron microscopy and transmission electron microscopy.The cast specimens contain CeMg_(12),Mg and Mg_(2)Ni phases,and the increase in Ni content results in an obvious growth of Mg_(2)Ni phase.The isothermal and non-isothermal hydrogenation and dehydrogenation kinetics of the experimental specimens were investi-gated using the Sievert apparatus,differential scanning calorimetry and thermal gravimetric analyzer.The activation energy may be calculated using the Arrhenius and Kissinger equations.The experimental alloys have been shown to have good activation properties,with a reversible hydriding and dehydriding capacities of around 5.0 wt.%in the first cycle.The initial dehydrogenation temperature of MgH_(2) decreases from 557.5 to 537.7 K with changing Ni content from 5 to 15 at.%.The dehydrogenation activation energy also reduces from 77.09 to 62.96 kJ/mol,which explains the improved hydrogen storage performance caused by Ni substitution.It can be shown that the impact of Ni on the decomposition enthalpy of MgH_(2) is quite modest,with the absolute enthalpy(ΔHr)only decreasing from 78.48 to 76.15 kJ/mol.

关键词： Mg-based alloy Ni content Hydrogen storage kinetics Thermodynamic property Activation energy

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Identifying coronary artery bypass grafting patients at high risk for adverse long-term prognosis using serial health-related quality of life assessments

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中华医学杂志(英文版) 2024年第9期137卷 1069-1077页

作者： Wang Juncheng Liu Hanning Yue Chao Yang Limeng Yang Kai zhao Yan Ren huan Zhang Ying Zheng Zhe National Clinical Research Center for Cardiovascular Diseases State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Cardiovascular Surgery Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Vascular Surgery Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Cardiac Surgery Wuhan Asia Heart Hospital Wuhan Hubei China

Background: Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients.Methods: The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes.Results: The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07–2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09–2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively).Conclusions: Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better

关键词： Coronary artery bypass grafting Coronary artery disease Prognosis Quality of life Short-Form 36 Risk factor Serial measurements

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A regression approach for seismic first-break picking

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Petroleum Science 2024年第3期21卷 1584-1596页

作者： huan Yuan San-Yi Yuan Jie Wu Wen-Jing Sang Yu-He zhao CNPC Key Laboratory of Geophysical Exploration China University of Petroleum (Beijing) Research Institute of Petroleum Exploration & Development—Northwest (NWGI) Key Laboratory of reservoir characterization of CNPCPetroChina

The picking efficiency of seismic first breaks(FBs) has been greatly accelerated by deep learning(DL)technology. However, the picking accuracy and efficiency of DL methods still face huge challenges in low signal-to-noise ratio(SNR) situations. To address this issue, we propose a regression approach to pick FBs based on bidirectional long short-term memory(Bi LSTM) neural network by learning the implicit Eikonal equation of 3D inhomogeneous media with rugged topography in the target region. We employ a regressive model that represents the relationships among the elevation of shots, offset and the elevation of receivers with their seismic traveltime to predict the unknown FBs, from common-shot gathers with sparsely distributed traces. Different from image segmentation methods which automatically extract image features and classify FBs from seismic data, the proposed method can learn the inner relationship between field geometry and FBs. In addition, the predicted results by the regressive model are continuous values of FBs rather than the discrete ones of the binary distribution. The picking results of synthetic data shows that the proposed method has low dependence on label data, and can obtain reliable and similar predicted results using two types of label data with large differences. The picking results of9380 shots for 3D seismic data generated by vibroseis indicate that the proposed method can still accurately predict FBs in low SNR data. The subsequent stacked profiles further illustrate the reliability and effectiveness of the proposed method. The results of model data and field seismic data demonstrate that the proposed regression method is a robust first-break picker with high potential for field application.

关键词： First-break picking Low signal-to-noise ratio Regression BiLSTM Traveltime Geometry Noisy seismic data

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Effects of Maillard reaction and its product AGEs on aging and age-related diseases

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Food Science and Human Wellness 2024年第3期13卷 1118-1134页

作者： huan Peng Yuqi Gao Chenye Zeng Rui Hua Yannan Guo Yida Wang zhao Wang Protein Science Key Laboratory of the Ministry of Education School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China

Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.

关键词： Maillard reaction Advanced glycation end products Physiologic aging Pathological aging Drug intervention

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HDPairFinder:A data processing platform for hydrogen/deuterium isotopic labeling-based nontargeted analysis of trace-level amino-containing chemicals in environmental water

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Journal of Environmental Sciences 2024年第2期136卷 583-593页

作者： Tingting zhao Kristin Carroll Caley B.Craven Nicholas J.P.Wawryk Shipei Xing Jian Guo Xing-Fang Li Tao huan Department of Chemistry Faculty of ScienceUniversity of British ColumbiaVancouver Campus2036 Main MallVancouverBritish ColumbiaV6T 1Z1Canada Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6G 2G3Canada

The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful analytical solution for nontargeted analysis of trace-level amino-containing chemicals in water samples.Given the huge amount of chemical information generated in HPLC-HRMS analysis,identifying all possible H/Dlabeled amino chemicals presents a significant challenge in data processing.To address this,we designed a streamlined data processing pipeline that can automatically extract H/D-labeled amino chemicals from the raw HPLC-HRMS data with high accuracy and efficiency.First,we developed a cross-correlation algorithm to correct the retention time shift resulting from deuterium isotopic effects,which enables reliable pairing of H-and D-labeled peaks.Second,we implemented several bioinformatic solutions to remove false chemical features generated by in-source fragmentation,salt adduction,and natural13C isotopes.Third,we used a data mining strategy to construct the AMINES library that consists of over 38,000 structure-disjointed primary and secondary amines to facilitate putative compound annotation.Finally,we integrated these modules into a freely available R program,HDPairFinder.R.The rationale of each module was justified and its performance tested using experimental H/D-labeled chemical standards and authentic water samples.We further demonstrated the application of HDPairFinder to effectively extract N-containing contaminants,thus enabling the monitoring of changes of primary and secondary N-compounds in authentic water samples.HDPairFinder is a reliable bioinformatic tool for rapid processing of H/D isotopic methyl labeling-based nontargeted analysis of water samples,and will facilitate a better understanding of N-containing chemical compounds in water.

关键词： Isotope labeling Nontargeted analysis Reactive N-compounds HPLC-HRMS Source water

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A Comprehensive Study of a Low-Grade Heat-Driven Cooling and Power System Based on Heat Current Method

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Journal of Thermal Science 2024年第4期33卷 1523-1541页

作者： zhao Tian XU Ronghong XIN Yonglin HE Kelun MA huan YUAN Mengdi CHEN Qun School of Energy Storage Science and Engineering North China University of Technology Key Laboratory for Thermal Science and Power Engineering of Ministry of Education Department of Engineering MechanicsTsinghua University

Combined cooling and power(CCP) system driven by low-grade heat is promising for improving energy efficiency.This work proposes a CCP system that integrates a regenerative organic Rankine cycle(RORC)and an absorption chiller on both driving and cooling fluid sides.The system is modeled by using the heat current method to fully consider nonlinear heat transfer and heat-work conversion constraints and resolve its behavior accurately.The off-design system simulation is performed next,showing that the fluid inlet temperatures and flow rates of cooling water as well as RORC working fluid strongly affect system performance.The off-design operation even becomes infeasible when parameters deviate from nominal values largely due to limited heat transfer capability of components,highlighting the importance of considering heat transfer constraints via heat current method.Design optimization aiming to minimize the total thermal conductance is also conducted.RORC efficiency increases by 7.9% and decreases by 12.4% after optimization,with the hot fluid inlet temperature increase from 373.15 to 403.15 K and mass flow rate ranges from 10 to 30 kg/s,emphasizing the necessity of balancing system cost and performance.

关键词： combined cooling and power system organic Rankine cycle absorption chiller cascade heat utilization heat current method off-design analysis

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Defect-manipulated magnetoresistance and above-room-temperature ferromagnetism in two-dimensional BaNi_(2)V_(2)O_(8)

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Chinese Chemical Letters 2024年第3期35卷 523-527页

作者： Pengfei Tan Chuanhui Zhu Jinjin Yang Shuang zhao Tao Xia Mei-huan zhao Tao Han Zheng Deng Man-Rong Li Key Laboratory of Bioinorganic and Synthetic Chemistry of Ministry of Education School of ChemistrySun Yat-sen UniversityGuangzhou 510006China School of Science and Engineering The Chinese University of Hong KongShenzhen 518172China Institute of Physics Chinese Academy of SciencesBeijing 100190China School of Science Hainan UniversityHaikou 570228China

The intricate correlation between multiple degrees of freedom and physical properties is a fascinating area in solid state chemistry and condensed matter physics.Here,we report a quantum-magnetic system BaNi_(2)V_(2)O_(8)(BNVO),in which the spin correlation was modulated by unusual oxidation state,leading to different magnetic behavior.The BNVO was modified with topochemical reduction(TR)to yield TR-BNVO with partially reduced valance state of Ni^(+)in the two-dimensional NiO_(6)-honeycomb lattice.Accordingly,the antiferromagnetic order is suppressed by the introduction of locally interposed Ni^(+)and oxygen vacancies,resulting in a ferromagnetic ground state with the transition temperature up to 710 K.A positive magnetoresistance(7.5%)was observed in the TR-BNVO at 40 K under 7 T.These findings show that topological reduction is a powerful approach to engineer low-dimensional materials and accelerate the discovery of new quantum magnetism.

关键词： Layered honeycomb oxide Topochemical reduction Oxygen vacancies Ferromagnetism Magnetoresistance

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Atmospheric chemistry of 2-nitrobenzaldehyde:Initiated by photo-excitation,OH-oxidation,and small TiO_(2) clusters adsorption catalysis

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Journal of Environmental Sciences 2024年第5期139卷 123-137页

作者： Feng-Yang Bai Xiang-huan Liu Ting-Ting Meng Zhou Yu Yi-Chen Wang Shuang Ni Zhen zhao Institute of Catalysis for Energy and Environment College of Chemistry and Chemical EngineeringShenyang Normal UniversityShenyang 110034China

The fate of 2-nitrobenzaldehyde(2-NBA)is of interest in atmospheric chemistry as it is a semi-volatile organic compound with high photosensitivity.This study presents a quantum chemical study of the gas-phase reactions of 2-NBA photo-excitation and OH-oxidation in the absence and presence of small TiO_(2) clusters.To further understand the unknown photolysis mechanism,the photo-reaction pathways of ground singlet state and the lying excited triplet state of 2-NBA were investigated including the initial and subsequent reactions of proton transfer,direct CO,NO_(2),and HCO elimination routes in the presence of O_(2) and NO.Meanwhile,the OH-mediated degradation of 2-NBA proceeded via five H-extraction and six OH-addition channels by indirect mechanism,which follows a succession of reaction steps initiated by the formation of weakly stable intermediate complexes.The H-extraction from the-CHO group was the dominant pathway with a negative activation energy of-1.22 kcal/mol.The calculated rate coefficients at 200–600 K were close to the experimental data in literature within 308-352 K,and the kinetic negative temperature independence was found in both experimental literature and computational results.Interestingly,2-NBA was favored to be captured onto small TiO_(2) clusters via six adsorption configurations formed via various combination of three types of bonds of Ti…O,Ti…C,and O…H between the molecularly adsorbed 2-NBA and TiO_(2) clusters.Comparison indicted that the chemisorptions of aldehyde oxygen have largest energies.The results suggested adsorption conformations have a respectable impact on the catalysis barrier.This study is significant for understanding the atmospheric chemistry of 2-nitrobenzaldehyde.

关键词： 2-nitrobenzaldehyde OH radical oxidation Rate coefficient Photolysis mechanism Adsorption catalysis

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