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Nanoparticle drug delivery system for the treatment of brain tumors:Breaching the blood–brain barrier

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2786-2789页

作者： Qiyu Tang Guo Zhao Hong Fang Yale Jiang Peiwen Ma Jiawei Zhoua Dongyan Liu Shujun Xing Gaoquan Li Nian Liu Huiyu Chen Shuhang Wang Ning Li clinical trial center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Chongqing Upgra Biotechnology Co. Ltd.Chongqing 401331China

To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in *** tumors encompass primary tumors originating in the brain and brain metastases(BM)that have been spread from cancer lesions of other ***,BM are the most prevalent intracranial malignant tumor affecting approximately 20%-40%of cancer patients2.

关键词： Nanoparticle Drug delivery system Blood-brain barrier Tumor Glioma

Filamentation and inhibition of prokaryotic CTP synthase with ligands

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mLife 2024年第2期3卷 240-250页

作者： Chenjun Guo Zixuan Wang Ji‐Long Liu School of Life Science and Technology ShanghaiTech UniversityShanghaiChina Department of Physiology Anatomy and GeneticsUniversity of OxfordOxfordUK Shanghai clinical Research and trial center ShanghaiChina

Cytidine triphosphate synthase(CTPS)plays a pivotal role in the de novo synthesis of cytidine triphosphate(CTP),a fundamental building block for RNA and DNA that is essential for *** is capable of directly binding to all four nucleotide triphosphates:adenine triphosphate,uridine triphosphate,CTP,and guanidine ***,CTPS can form cytoophidia in vivo and metabolic filaments in vitro,undergoing regulation at multiple *** is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic *** cryo-electron microscopy,we determined the structure of Escherichia coli CTPS(ecCTPS)filament in complex with CTP,nicotinamide adenine dinucleotide(NADH),and the covalent inhibitor 6-diazo-5-oxo-L-norleucine(DON),achieving a resolution of *** constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis,providing an evolutionary perspective on CTPS filament *** computational analysis revealed a solvent-accessible ammonia tunnel upon DON *** comparative structural analysis,we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic *** biochemical assays and structural analysis,we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on *** results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

关键词： CTP synthase Cryo-electron microscopy cytoophidium metabolic filament species specific inhibition

Structural disruption of melanin-like polymers with boosted UV protection

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Science China Chemistry 2024年第5期67卷 1653-1663页

作者： Zhen Yang Xianheng Wang Wanjie Bai Zikun Zou Haoxing Wu Yiwen Li Department of Radiology Huaxi MR Research CenterFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China

Manipulating the energy structure of materials represents an efficient way to regulate their light absorption behaviors. For example, constructing donor-acceptor(D-A) structures to increase the polarizability and reduce the energy bandgap of local molecules has been widely used in the field of organic photovoltaics with ordered structures. Remarkably, even in disordered and chaotic systems such as melanin-like polydopamine(PDA), visible and near-infrared light absorption can be significantly improved using this strategy. However, there has been a noticeable dearth of research on the ultraviolet(UV) light absorption regulation of bioinspired polymers with disordered and chaotic architectures by tailoring the D-A microstructures. In this study, a series of benzoheterocyclic molecules with strong electron-donating features screened by molecular simulation calculations were involved in disrupting the D-A structures within PDA. The destruction of D-A structures promoted the increase of the energy band gap and finally boosted the UV absorption of PDA. The resulting PDA nanoparticles with enhanced UV absorption were further employed to fabricate UV shielding composite films to protect the growth of plants from harmful UV radiation. This research may open up new avenues for structural disruption of bioinspired polymers for enhanced photoprotection applications.

关键词： melanin-like polymers polydopamine D-A structure UV absorption photoprotection

Synthetic fungal melanin UV absorbers

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Science China Chemistry 2024年第9期67卷 3098-3110页

作者： Chao Wang Rong Zhang Jianhua Zhang Xueqian Zhang Hengjie Zhang Huan Cao Zhen Yang Yiwen Li College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China Department of Radiology Huaxi MR Research CenterFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

Agents with robust ultraviolet(UV)absorption capabilities play a vital role in safeguarding organisms and inorganic materials from UV ***,the synthetic procedures towards these UV absorbers are usually lengthy and complicated,accompanied by undesirable side reactions and the generation of toxic *** nature,allomelanin,a class of melanins variant found in melanized fungi near the Chernobyl nuclear power plant,plays crucial roles in the cell wall of melanized fungi,offering resistance to harsh external environments and promising UV resistance ***,allomelanin can be rapidly biosynthesized via the polymerization of 1,8-dihydroxynaphthalene in presence of enzymes in *** by this,we report here a green enzymatic polymerization strategy to efficiently and eco-friendly synthesize polydihydroxynaphthalene(PDHN)-based artificial allomelanin nanoparticles(NPs)with interesting *** calculations and experimental results demonstrated that the PDHN NPs exhibited excellent UVabsorption capacity,surpassing another widely used artificial melanin,polydopamine(PDA).Moreover,the light absorption mechanism of PDHN NPs was systematically elucidated for the first ***,the PDHN NPs were incorporated with polyvinyl alcohol(PVA)to create an anti-aging composite film with significantly enhanced UV shielding *** potential of these composite films in safeguarding plants from UV damage was meticulously ***,these PDHN NPs were first found to produce hydroxyl radicals(·OH)under UV irradiation,offering antibacterial properties that expand their potential applications.

关键词： melanin artificial allomelanin nanoparticles green synthesis UV absorption antibacterial

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

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Food Science and Human Wellness 2024年第3期13卷 1258-1270页

作者： Qishan Wang Bin Liu Xianping Li Junying Zhao Zongshen Zhang Weicang Qiao Xinyue Wei Lijun Chen School of Bioengineering Dalian Polytechnic UniversityDalian 116034China National Engineering Research center of Dairy Health for Maternal and Child Beijing Sanyuan Foods Co.Ltd.Beijing 100163China Beijing Engineering Research center of Dairy Beijing Sanyuan Foods Co.Ltd.Beijing 100163China

The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are ***,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral *** 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical *** results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid ***,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and ***,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase ***,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

关键词： Dairy products Calcium Vitamin D Bone turnover markers Gut microbiota Postmenopausal osteoporosis

A biocompatible Horner-Wadsworth-Emmons(HWE)reaction triggered by a bioorthogonal proximity-induced platform

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Chinese Chemical Letters 2024年第8期35卷 217-220页

作者： Yayue Wang Haojie Yang Jie Li Qiao Kong Siming Zhou Hongbao Sun Lili Pan Qiyong Gong Ping Feng Haoxing Wu Department of Radiology and Huaxi MR Research center(HMRRC) Functional and Molecular Imaging Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan UniversityChengdu 610041China Department of Nuclear Medicine Laboratory of Clinical Nuclear MedicineWest China HospitalSichuan UniversityChengdu 610041China Reseacrch Unit of Psychoradiology Chinese Academy of Medical SciencesChengdu 610041China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610041China clinical trial center and National Medical Products Administration Key Laboratory for clinical Research and Evaluation of Innovative Drugs West China HospitalSichuan UniversityChengdu 610041China

Here,we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity,thereby facilitating the discovery and optimization of biocompatible *** this platform,we achieve a Horner-Wadsworth-Emmons(HWE)reaction under physiological conditions,generating a fluorophore in situ with a yield of up to 93%.This proximity platform should facilitate the discovery of various types of biocompatible reactions,making it a versatile tool for biomedical applica-tions.

关键词： Biocompatible reactions Horner-Wadsworth-Emmons reaction Bioorthogonal reactions Tetrazines Proximity effects

Insights on ZEB1-AS1:emerging role from cancer to neurodegeneration

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Neural Regeneration Research 2024年第6期19卷 1187-1188页

作者： Stephana Carelli Federica Rey Erika Maghraby Cristina Cereda Pediatric Research center“Romeo ed Enrica Invernizzi” Department of Biomedical and Clinical SciencesUniversity of MilanMilanItaly center of functional Genomics and Rare Diseases Department of PediatricsBuzzi Children’s HospitalMilanItaly Department of Biology and Biotechnology“L.Spallanzani” University of PaviaPaviaItaly

Implications for lncRNAs in the central nervous system:Transcriptional dysregulation is a key contributor to the pathogenesis of a wide range of diseases and long non-coding RNAs(lncRNAs)are highly expressed in the nervous ***,amongst the over 50,000 lncRNAs expressed in the human genome,more than 40%are specifically expressed in the brain where their roles in brain development,neuron functions,maintenance.

关键词： ZEB1 diseases pathogenesis

Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models

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World Journal of Gastroenterology 2024年第9期30卷 1164-1176页

作者： Yan-Li Jiang Juan Li Peng-Fei Zhang Feng-Xian Fan Jie Zou Pin Yang Peng-Fei Wang Shao-Yu Wang Jing Zhang Department of Magnetic Resonance Imaging The Second Hospital&Clinical Medical SchoolLanzhou UniversityLanzhou 730030Gansu ProvinceChina Second clinical School Lanzhou UniversityLanzhou 730030Gansu ProvinceChina Gansu Province clinical Research center for functional and Molecular Imaging The Second Hospital&Clinical Medical SchoolLanzhou UniversityLanzhou 730030Gansu ProvinceChina Department of Hepatology The Second Hospital&Clinical Medical SchoolLanzhou UniversityLanzhou 730030Gansu ProvinceChina MR Scientific Marketing Siemens HealthineersXi’an 710065Shaanxi ProvinceChina

BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver ***,its diagnostic performance is inconsistent among ***,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one *** To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic *** This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy *** participants underwent multi-b value *** main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and *** CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis *** areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was *** combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver *** combined index of CTRW paramet

关键词： Liver fibrosis Magnetic resonance imaging Diffusion-weighted magnetic resonance Liver biopsy Significant fibrosis