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Acta Pharmaceutica Sinica B 2024年第6期14卷 2716-2731页

作者： Yang Tong Pei An Puxian Tang Rui Mu Yuteng Zeng Hang Sun Mei Zhao Ziyan Lv Pan Wang Wanjun Han Chunshan Gui Xuechu Zhen Liang Han Jiangsu Key Laboratory of Neuropsychiatric Diseases and college of pharmaceutical Sciences Soochow UniversitySuzhou 215123China Jiangsu Province engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China

Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid *** inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood-tumor barrier(BTB).BTB activates its Wnt signaling to maintain barrier properties,e.g.,Mfsd2a-mediated BTB low ***,we reported VCAM-1-targeting nano-wogonin(W@V-NPs)as an adjuvant of nano-orlistat(O@V-NPs)to intensify drug delivery and inhibit lipogenesis of brain metastases.W@V-NPs were proven to be able to inactivate BTB Wnt signaling,downregulate BTB Mfsd2a,accelerate BTB vesicular transport,and enhance tumor accumulation of O@*** the ability to specifically kill cancer cells in a lipid-deprived environment with IC_(50) at 48 ng/mL,W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model *** combination did not induce brain edema,cognitive impairment,and systemic toxicity in healthy *** Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.

关键词： Lipogenesis Brain metastases Blood-tumor barrier Wnt signaling Drug delivery Fatty acid synthase Nanoparticles Combination therapy

Structure-guided isolation of anti-neuroinflammatory sesquiterpene coumarins from Ferula sinkiangensis

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Chinese Journal of Natural Medicines 2024年第7期22卷 643-653页

作者： DANG Wen GUO Tingting ZHOU Di MENG Qingqi FANG Mingxia CHEN Gang LIN Bin HOU Yue LI Ning School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning ProvinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110016China college of Life and Health Sciences Northeastern UniversityShenyang 110004China School of pharmaceutical engineering Shenyang Pharmaceutical UniversityShenyang 110016China

The resin of Ferula sinkiangensis has been traditionally utilized for treating gastrointestinal disorders,inflammation,tumors,various cancers,and alopecia *** primary bioactive constituents,sesquiterpene coumarins,have demonstrated notable therapeutic potential against *** this study,a structure-guided fractionation method was used to isolate nine novel sesquiterpene coumarins from the resin of *** compounds were characterized and structurally elucidated using comprehensive physicochemical and spectroscopic techniques,including calculated electronic circular dichroism(ECD).Anti-neuroinflammatory assays revealed that compounds 2,3,and 6 significantly inhibited nitric oxide(NO)production in lipopolysaccharide(LPS)-stimulated BV2 microglial cells,with IC_(50)values ranging from 1.63 to 12.25μmol·L^(−1).

关键词： Ferula sinkiangensis Sesquiterpene coumarins Structure elucidation Anti-neuroinflammatory activity

Biomimetic microchannel network with functional endothelium formed by sacrificial electrospun fibers inside 3D gelatin methacryloyl(GelMA)hydrogel models

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Journal of Zhejiang University-Science A(Applied Physics & engineering) 2024年第1期25卷 79-96页

作者： Haoyu SUN Haiyang MA Li WANG Yang LIU Tian HOU Wenjie TANG Qing YU Meiwen AN Meiling WEN Institute of Biomedical engineering College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China

Three-dimensional(3D)hydrogel models play a crucial role in tissue engineering for promoting tissue regeneration.A biomimetic microchannel network system in the 3D hydrogel model is necessary for optimal cellular *** report describes the preparation of a biomimetic hydrogel scaffold with an internal microchannel network,using electrospinning techniques and the sacrificial template method for 3D cell *** and cavities were created within the gelatin methacryloyl(GelMA)hydrogel by sacrificing polyvinyl alcohol(PVA)electrospun fibers(>10µm),resulting in the creation of microvessel-like *** characterizations,swelling properties,and biodegradation analysis were conducted to investigate the feasibility of a biomimetic microchannel network hydrogel scaffold for 3D cell culture *** to pure GelMA hydrogel,the hydrogel with microchannels promoted cell proliferation,adhesion,and endothelial tube ***,the results confirmed that the biomimetic microchannel network scaffold had a major impact on the distribution and arrangement of human umbilical vein endothelial cells(HUVECs)and can enable the formation of artificial microvasculature by the culture of HUVECs and cell media perfusion.

关键词： Biomimetic scaffold Photocrosslinking Microchannel network Tissue engineering Artificial microvascular

The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1400-1411页

作者： Shuo Wang Tian Liu Yuetong Huang Chaoying Du Danping Wang Xiyan Wang Qingzhi Lv Zhonggui He Yinglei Zhai Bingjun Sun Jin Sun Wuya college of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Binzhou Medical UniversityBinzhou 256600China

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly *** the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug *** study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’*** extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative *** use of C_(20) can balance efficacy and *** results provide a great reference for the rational design of prodrug nanoassemblies.

关键词： Prodrugs Nanoassemblies Self-assembly Branched-chain fatty alcohols Disulfide bond Docetaxel Efficacy Safety

Adsorption,in vitro digestion and human gut microbiota regulation characteristics of three Poria cocos polysaccharides

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Food Science and Human Wellness 2024年第3期13卷 1685-1697页

作者： Fangming Zhang Hui Zheng Tao Zheng Pan Xu Yao Xu Yuxin Cao Fan Jia Yiqiong Zeng Yubing Fan Kai He Xinwen Dai Fengfei Hou Yong Yang college of Pharmacy Hunan University of Chinese MedicineChangsha 410208China School of pharmaceutical Science Hunan University of MedicineHuaihua 418000China Hunan Fuling engineering Technology Research Center Huaihua 418100China

Poria cocos(PC)is a famous traditional Chinese medicine(TCM)and a widely used healthcare ingredient,which has antiobesity,enhancing immunity and improving sleep ***,only water-soluble poria polysaccharide(WSP)is extracted and applied for clinical application,while insoluble polysaccharide(alkali-soluble poria polysaccharide,ASP)is discarded as herb ***,the whole PC has also been historically utilized as functional herbal *** the beneficial role of dietary fiber and the traditional use of PC,ASP may also contribute substantially to the therapy function of *** to WSP,little attention has been paid to ASP and ASP modified product carboxymethyl poria polysaccharide(CMP)which has been used as an antitumor adjuvant *** this study,the oil,cholesterol,metal ions and polyphenols adsorption ability,in vitro simulated digestive and the gut microbiota fermentation characteristics of WSP,ASP and CMP were studied to evaluate the functional values of three *** polysaccharides(PCPs).The results showed that all three PCPs had good adsorption capacity on cholesterol,polyphenols and metal ions(Cd^(2+)/Zn^(2+)/Mg^(2+)),among which ASP showed the highest capacity than WSP and *** adsorption capacity of all three PCPs on heavy metal ions(Cd^(2+)/Zn^(2+))was stronger than that of non-heavy metal ions(Mg^(2+));The in vitro digestibility of all three PCPs was very low,but WSP was slightly higher than ASP and CMP;Moreover,the indigestible residue of all three PCPs could improve the richness and diversity of gut microbiota,among which ASP had the greatest *** general,ASP and CMP could significantly promote the proliferation of some probiotics and inhibit the growth of some harmful *** gut microbiota diversity of CMP was reduced,but the richness of probiotics,especially Parabacteroides distasonis was significantly enhanced compared with the ASP group,and the growth of harmful bacteria Klebsiella pneumoniae was inh

关键词： Poria cocos polysaccharides Alkali-soluble poria polysaccharide Carboxymethyl poria polysaccharide Adsorption characteristics In vitro simulated digestion In vitro simulated gut microbiota fermentation

Achieving exceptionally high strength and rapid degradation rate of Mg-Er-Ni alloy by strengthening with lamellar γ' and bulk LPSO phases

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Journal of Materials Science & Technology 2024年第1期168卷 88-102页

作者： Chaoneng Dai Jingfeng Wang Yuanlang Pan Kai Ma Yinhong Peng Ye Wang Danqian Wang Chunhua Ran Jinxing Wang Yanlong Ma college of Chemistry and Chemical engineering Chongqing UniversityChongqing 401331China college of Materials Science and engineering Chongqing UniversityChongqing 400044China National engineering Research Center for Magnesium Alloys Chongqing 400044China college of Materials Science and engineering Chongqing University of TechnologyChongqing 400054China

As-extruded Mg-Er-Ni alloys with different volume fractions of long-period stacking ordered(LPSO)phase and density of lamellar γ' phase were prepared,and the microstructure,mechanical,and degradation properties were *** the bulk LPSO phase and the lamellar γ' phase,and controlling the dynamic recrystallization processes during deformation by adjusting the volume fraction of LPSO and the density of the γ' phase,a synergistic increase in strength and degradation rate can be *** the one hand,the increase in corrosion rate was related to the increased volume fraction of the bulk LPSO phase and the densities of the lamellar γ' phase,which provide more galvanic ***,high densities of the lamellar γ' phase can provide more corrosion interface by inhibiting the recrystallization process to refine dynamic recrystallized(DRXed)grains during the hot *** the other hand,the ultimate tensile strength(UTS)and tensile yield strength(TYS)of the Mg-Er-Ni alloy increased from 345 and 265 MPa to 514 MPa and 358 MPa,respectively,which was mainly attributed to grain boundary and texture strengthening,bulk LPSO phase and lamellar γ' phase ***,Mg^(-1)4Er-4Ni alloy,which contains the highest volume fraction bulk LPSO phase and the densities of lamellar γ' phase,re-alized a synergistic enhancement of strength and degradation *** UTS,TYS,and degradation rate of Mg^(-1)4Er-4Ni were 514 MPa,358 MPa,and 142.5 mg cm^(-2)h^(-1)(3 wt%KCl solution at 93◦C),*** research provides new insight into developing Mg alloys with high strength and degradation rates for fracturing tool materials in the application of oil and gas exploitation in harsh environments.

关键词： Mg-Er-Ni alloy Lamellarγ'and bulk LPSO phases Rapid degradation rate High strength Mechanical and corrosion mechanism

Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

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Oncology Research 2024年第5期32卷 877-897页

作者： KARAN WADHWA PAYAL CHAUHAN SHOBHIT KUMAR RAKESH PAHWA RAVINDER VERMA RAJAT GOYAL GOVIND SINGH ARCHANA SHARMA NEHA RAO DEEPAK KAUSHIK Department of pharmaceutical Sciences Maharshi Dayanand UniversityRohtak124001India Department of pharmaceutical Technology Meerut Institute of Engineering and Technology(MIET)NH-58Delhi-Roorkee HighwayMeerut250005India Institute of pharmaceutical Sciences Kurukshetra UniversityKurukshetra136119India Department of pharmaceutical Sciences Chaudhary Bansi Lal UniversityBhiwani127021India MM college of Pharmacy Maharishi Markandeshwar(Deemed to be University)Mullana-AmbalaHaryana133207India Delhi pharmaceutical Sciences and Research University(DIPSAR) Delhi Pharmaceutical Sciences and Research UniversityNew Delhi110017India

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive *** high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the ***:Recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation ***:Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several ***:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM *** of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

关键词： Glioblastoma Brain tumor Blood-brain barrier Liposomes Metallic nanoparticles Nanocarriers

The guest CH_(3)CN molecule triggers solid-state photochromism in a Cu_(2)I_(2)-based MOF for advanced time-dependent encryption and inkless erasable printing

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Chinese Chemical Letters 2024年第3期35卷 532-537页

作者： Meng-Juan Wang Bo Li Yong-Li Wei Shu-Na Zhao Shuang-Quan Zang Henan Key Laboratory of Crystalline Molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsGreen Catalysis Centerand College of ChemistryZhengzhou UniversityZhengzhou 450001China college of Chemistry and pharmaceutical engineering Nanyang Normal UniversityNanyang 473061China

It remains a big challenge to develop solid-state stimuli-responsive materials for time-dependent information encryption and inkless erasable printing with long retention ***,a 2D Cu_(2)I_(2)-based MOF with photoresponsive spiropyran(SP)groups orderly installed on its skeleton is *** structural isomerization from SP to colored merocyanine(MC)form can be triggered by removing the CH_(3)CN ***,the degree of structural isomerization and the retention time can be adjusted by controlling the amount of CH_(3)CN guests,exhibiting dynamic photochromic behavior with multicolor states and tunable retention *** on these advantages,time-dependent information encryption is successfully ***,the long retention time(>72 h)of the MC form under daylight conditions in the CH_(3)CN-removed Cu_(2)I_(2)-based MOF and good repeatability make it promising in various applications,such as temporary calendars,price-cards,billboards,and reusable identity *** work provides a novel design strategy to fabricate multi-functional MOF-based smart materials for challenging applications of time-dependent information encryption and inkless erasable printing.

关键词： Stimuli-responsive materials Spiropyran Solid-state photochromism Time-dependent encryption Inkless erasable printing

Separation identification of a neural fuzzy Wiener–Hammerstein system using hybrid signals

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Frontiers of Information Technology & Electronic engineering 2024年第6期25卷 856-868页

作者： Feng LI Hao YANG Qingfeng CAO college of Electrical and Information engineering Jiangsu University of TechnologyChangzhou 213001China college of Electrical Energy and Power EngineeringYangzhou UniversityYangzhou 225127China

A novel separation identification strategy for the neural fuzzy Wiener–Hammerstein system using hybrid signals is developed in this *** Wiener–Hammerstein system is described by a model consisting of two linear dynamic elements with a nonlinear static element in *** static nonlinear element is modeled by a neural fuzzy network(NFN)and the two linear dynamic elements are modeled by an autoregressive exogenous(ARX)model and an autoregressive(AR)model,*** the system input is Gaussian signals,the correlation technique is used to decouple the identification of the two linear dynamic elements from the nonlinear ***,based on the input and output of Gaussian signals,the correlation analysis technique is used to identify the input linear element and output linear element,which addresses the problem that the intermediate variable information cannot be measured in the identified Wiener–Hammerstein ***,a zero-pole match method is adopted to separate the parameters of the two linear ***,the recursive least-squares technique is used to identify the nonlinear element based on the input and output of random signals,which avoids the impact of output *** feasibility of the presented identification technique is demonstrated by an illustrative simulation example and a practical nonlinear *** results show that the proposed strategy can obtain higher identification precision than existing identification algorithms.

关键词： Wiener-Hammerstein system Neural fuzzy network Correlation analysis technique Hybrid signals Separation identification

Smad8 is involvement in follicular development via the regulation of granulosa cell growth and steroidogenesis in mice

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BIOCELL 2024年第1期48卷 139-147页

作者： DAOLUN YU DEYONG SHE KAI GE LEI YANG RUINA ZHAN SHAN LU YAFEI CAI college of Biotechnology and pharmaceutical engineering West Anhui UniversityLu’an237012China Lu’an Academy of Agricultural Sciences Lu’an237001China college of Life Sciences Anhui Normal UniversityWuhu241000China college of Animal Science and Technology Nanjing Agricultural UniversityNanjing210095China

Background:SMAD family proteins(SMADs)are crucial transcription factors downstream of transforming growth factor beta(TGF-ß)/SMAD signaling pathways that have been reported to play a pivotal role in mammalian ***,the role of SMAD family member 8(SMAD8,also known as SMAD9),a member of the SMAD family,in mammalian reproduction remains ***:We employed RNA interference techniques to knock down Smad8 expression in mouse granulosa cells(GCs)to investigate the effects of Smad8 on GC growth and ***:Our findings revealed a significant decrease in the proliferative capacity and a substantial increase in the apoptosis rate of GCs after transfection with Smad8-siRNA for 48 *** hormone assays demonstrated a significant decrease in estradiol(E2)levels,whereas progesterone(P4)remained *** mechanistic analysis showed that the mRNA expression of proliferating cell nuclear antigen(Pcna),Cyclin D2,cell cycle-dependent kinase 4(Cdk4),B-cell lymphoma-2(Bcl-2),estrogen receptor(Er),luteinizing hormone receptor(Lhr)and cytochrome P450 family 19 subfamily A member 1(Cyp19a1)significantly ***,the mRNA of cysteine aspartate proteinase 3(Caspase 3)significantly increased,wheras Bcl2-associated X(Bax),folliclestimulating hormone receptor(Fshr)and cytochrome P450 family 11 subfamily A member 1(Cyp11a1)remained unchanged compared to the ***:This study indicates that Smad8 knockdown inhibits cell proliferation,promotes apoptosis,reduces Er and Lhr transcription,and decreases E2 production in mouse *** findings suggest that Smad8 may serve as a novel genetic marker for mammalian reproduction.

关键词： Mouse Smad8 RNA interference Granulosa cells Growth and steroidogenesis