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Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

World Journal of Gastroenterology 2024年第3期30卷 268-279页

作者： Lie-Qi Tang Johnathan Fraebel Shi Jin Steven P Winesett Jane Harrell wen-Han Chang Sam Xianjun cheng Department of Pediatrics University of FloridaGainesvilleFL 32610United States College of Medicine University of FloridaGainesvilleFL 32610United States Applied Physiology and Kinesiology University of FloridaGainesvilleFL 32610United States Brain Rehabilitation Research Center Malcom Randall VA Medical CenterGainesvilleFL 32610United States Department of Medicine Endocrine Research UnitVeterans Affairs Medical CenterUniversity of CaliforniaSan FranciscoSan FranciscoCA 94121United States Department of Pediatric Gastroenterology Hepatologyand NutritionUniversity of Florida Shands Children’s HospitalGainesvilleFL 32608United States

BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous ***-sensing receptor(CaSR)inhibits both *** latter has been well documented in vitro but not in *** hypothesis to be tested was that activating CaSR inhibits diarrhea in *** To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in *** CTX was given orally to C57BL/6 mice to induce *** and calci-mimetic R568 were used to activate *** maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal *** verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR *** outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight *** CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in ***,calcium and R568 were each able to ameliorate diarrhea when applied to diseased *** CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global *** advances in diarrhea research,few have been made in the realm of diarrhea *** therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by *** is no cost-effective therapeutic for *** and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might

关键词： Cholera Enteric nervous system Secretory diarrhea Oral rehydration solution Calcium-sensing receptor Gene knockout

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Network Pharmacology of Xian-Lian-Jie-Du Decoction in Ameliorating Colorectal Cancer

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 83-92页

作者： Ming-Xia Zhao cheng-Lin Song Qin-Chang Zhang Hao-Jie Du Shu-Qiong Zhang Yu-Xian Shen Yang Sun Hai-Bo cheng wen Lv Department of Pharmacy School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhuiChina Department of Biopharmaceutical Research Institute Anhui Medical UniversityHefeiAnhuiChina Department of Pharmaceutical Analysis State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijingChina Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor First Clinical CollegeNanjing University of Chinese MedicineNanjingJiangsuChina Deparment of Biotechnology and Pharmaceutical Sciences State Key Laboratory of Pharmaceutical BiotechnologySchool of Life SciencesNanjing UniversityNanjingJiangsuChina Deparment of Gynecology Institute of Traditional Chinese Medicine of Zhejiang ProvinceTongde Hospital of Zhejiang ProvinceHangzhouZhejiangChina

Objective:In this study,we screened for therapeutic targets of the Xian-Lian-Jie-Du decoction(XLJDD)for colorectal cancer(CRC)and explored the underlying mechanisms using network pharmacology ***:Genes associated with CRC were collected from the Gene Cards *** names of the active compounds of XLJDD were used as keywords in the“chemical name”in the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database to search the *** protein-protein interaction(PPI)network was constructed using Cytoscape *** Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to identify key target ***:A total of 234 XLJDD-related targets and 250 cross-targets between XLJDD and CRC were collected based on the TCMSP and HIT 2.0 databases.A PPI network constructed based on the STRING database revealed interactions for all 250 *** network results revealed TP53,MYC,CCND1,AKT1,CASP3,and STAT3 as core potential *** pathway analysis of the 250 potential XLJDD targets for CRC in the Metascape database was performed using RStudio *** top 12 gene ratio aggregated analysis results were visualized in bubble *** interleukin(IL)-17 signaling pathway had the highest correlation with the tumor necrosis factor(TNF)signaling ***:XLJDD may be effective in ameliorating CRC by controlling inflammatory factors related to the IL-17 and TNF pathways and targeting proto-oncogenes and tumor suppressor genes,including MYC,CCND1,CTNNB1,and TP53.

关键词： Colorectal cancer network pharmacology Xian-Lian-Jie-Du decoction

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Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer

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Current Medical Science 2024年第4期44卷 833-840页

作者： Jun-he CHEN cheng-ming WEI Qian-yu LIN Zi WANG Fu-ming ZHANG Mei-na SHI wen-jian LAN Chang-gang SUN Wan-jun LIN wen-zhe MA State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao999078China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou510006China College of Traditional Chinese Medicine Weifang Medical UniversityWeifang261053China

Objective Colorectal cancer(CRC),a prevalent malignancy worldwide,has prompted extensive research into anticancer *** Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological *** study investigated the effects of Notopterygium incisum,a traditional Chinese medicine named Qianghuo(QH),on CRC cells and the underlying *** The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and *** iodide(PI)staining was utilized to detect cell cycle progression,and PE Annexin V staining to detect *** blotting was conducted to examine the levels of apoptotic proteins,including B-cell lymphoma 2-interacting mediator of cell death(BIM),B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(BAX)and cleaved caspase-3,as well as BIM stability after treatment with the protein synthesis inhibitor *** expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced *** in vivo effects of QH extract on tumor growth were observed using a xenograft ***,APC^(Min+)mice were used to study the effects of QH extract on primary intestinal *** QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation,perturbation of cell cycle progression,and induction of ***,QH extract significantly increased the stability of BIM proteins,which undergo rapid degradation under unstressed *** of BAX,the downstream effector of BIM,significantly rescued QH-induced ***,the in vitro effect of QH extract was recapitulated in *** extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APC^(Min+)*** QH extract

关键词： Notopterygium incisum colorectal cancer apoptosis B-cell lymphoma 2-interacting mediator of cell death

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Factors controlling the metal fertilization of granitic magma: Constraints from amphibole and biotite geochemistry of the Shangcheng pluton， Dabie orogen， Central China

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Journal of Earth Science 2024年

作者： cheng-Lai Deng Hui-Min Su Wu Li wen-Tian Li State Key Laboratory of Geological Processes and Mineral Resources， Collaborative Innovation Center for Exploration of Strategic Mineral Resources， School of Earth Resources， China University of Geosciences Wuhan School of Resources and Geosciences， China University of Mining and Technology

It is very common for similar granitoids to be emplaced in the same tectonic region， with some being metal-fertilized while others are barren. The reasons for this are still not clear. Here， we take the Shangcheng pluton as an example. This pluton occurs close to the giant Shapinggou porphyry Mo deposit， and we use amphibole and biotite geochemistry as sensitive tracers to explore this issue. The Shangcheng granitoids comprise the Sigudun （SGD） and Shiguwa （SGW） units， with emplacement ages ranging from 140 ± 3 Ma to 134 ± 2.4 Ma， as revealed by titanite U-Pb dating. The geochemical data of amphibole and biotite indicate that the magma intruded from depths of ～3.3 km to ～2.3 km with increasing oxygen fugacity. The modeled results indicate that water content is an essential factor for metal fertilization， as the Shangcheng pluton has a lower water content than the Shapinggou Mo-bearing granite. The Shangcheng pluton is also characterized by fluorine-poor conditions， with lower halogen fugacity values of IV（F） and log (f H2O/f HF)fluid. In contrast， the increasing Y/Ho and Nb/Ta ratios of the Shapinggou Mo-bearing granite indicate the F-rich nature of the fertilized Shapinggou magma， and its lower Zr/Hf and K/Rb ratios suggest a greater magma differentiation. Therefore， water-poor and F-poor magma， in combination with low-degree fractional crystallization， may be the major controlling factors responsible for the Mo-barren nature of the Shangcheng pluton.

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Analysis of multi-objective optimisation method for main insulation structure configuration scheme of valve-side winding of ultra-high voltage converter transformer considering multi-field coupling

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High Voltage 2024年第2期9卷 296-308页

作者： Lijun Yang Zhidong cheng Li cheng Ruijin Liao State Key Laboratory of Power Transmission Equipment Technology School of Electrical EngineeringChongqing UniversityChongqingChina

Because DC conductivities of oil-paper materials can be easily affected by electric field and temperature,the electrical properties under electro-thermal coupling of oil-paper materials should be considered when optimising the insulation structure of valve-side winding of the converter *** on the finite element multi-physical field coupling simulation,the multi-objective optimisation of main insulation structure of valve-side winding is carried *** view of the high time consuming of multi-physical field calculation and the actual needs of an insulation structure optimisation,the Kriging method and technique for order preference by similarity to the ideal solution(TOPSIS)method are introduced,and combines them with NSGA-II to obtain a joint algorithm that can be used for the optimisation of insulation structure of the converter *** using the joint algorithm of multi-objective optimisation,the insulation structure configuration scheme of valve-side winding is *** can be seen from the experiment result that,on the one hand,the joint algorithm adopted can obtain the insulation structure configuration scheme that meets the design *** the other hand,when facing the configuration scheme optimisation under multi-field coupling,the computational time required by this method is only 0.15%of that required by original genetic algorithm.

关键词： converter insulation coupling

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CD3ε of a pan T cell marker involved in mouse Aspergillus fumigatus keratitis

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 616-624页

作者： wen-Hao Shi Li-Mei Wang Hai-Jing Yan Shi-Long Liu Xian Yang Xue-JiaoYang cheng-Ye Che Department of Ophthalmology the Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina Weifang Medical University Weifang 261053Shandong ProvinceChina Eye Hospital of wenzhou Medical University Wenzhou 325027Zhejiang ProvinceChina Department of Medical Engineering the Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

AIM:To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus(***)keratitis in mice and the role of innate and adaptive immunity in ***:Mice models of *** keratitis were established by intra-stromal injection and corneal epithelial *** injections of natamycin,wedelolactone,LOX-1 inhibitor(poly I)or Dectin-1 inhibitor(laminarin)were used to treat mice with *** *** were pretreated by intraperitoneal injection of anti-mouse CD3ε.We observed the corneal infection of mice under the slit lamp microscope and made a clinical *** protein expression of CD3ε and interleukin-10(IL-10)was determined by Western ***:With the disease progresses,the degree of corneal opacity and edema *** the intrastromal injection models,CD3εprotein expression began to increase significantly on the 2^(nd) ***,in the scraping epithelial method models,CD3ε only began to increase on the 3^(rd) *** natamycin treatment,the degree of corneal inflammation in mice was significantly attenuated on the 3^(rd) *** wedelolactone treatment,the severity of keratitis *** the amount of CD3ε protein was also reduced,compared with the control *** inhibiting LOX-1 and Dectin-1,there was no significant difference in CD3ε production compared with the control *** inhibiting CD3ε,corneal ulcer area and clinical score increased,and IL-10 expression was ***:As a pan T cell marker,CD3ε participate in the adaptive immunity of *** keratitis in *** our mice models,the corneas will enter the adaptive immune stage *** regulating IL-10,CD3ε exerts antiinflammatory and repairs effects in the adaptive immune stage.

关键词： CD3ε adaptive immunity Aspergillus fumigatus keratitis interleukin-10

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Properties and microstructure of copper–titanium alloys with magnesium additions

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Rare Metals 2024年第5期43卷 2290-2299页

作者： Lue Huang Li-Jun Peng Jiang Li Xu-Jun Mi Gang Zhao Guo-Jie Huang Hao-Feng Xie Yi-cheng Cao wen-Jing Zhang Zhen Yang State Key Laboratory of Nonferrous Metals and Processes GRINM Group Co.Ltd.Beijing 100088China GRIMAT Engineering Institute Co. LtdBejing 101407China School of Materials Science and Engineering Northeastern UniversityShenyang110000China General Research Institute for Nonferrous Metals Beijing 100088China China Academy of Space Technology Beijing 100094China China Nonferrous Metals Mining Group(Tianjin)Co.Ltd Tianjin 3001llChina

The volume fractions and morphology of precipitates in precipitation-strengthened Cu-Ti alloys,which precipitate mainly as continuous and discontinuous precipitates,are important for the application of the *** study employed hardness and electrical conductivity tests transmission electron microscopy(TEM),atom probe tomography(APT),and first-principles calculations to demonstrate that the addition of Mg is effective for accelerating nanosized continuousβ'-Cu_(4)Ti precipitation as well as for suppressing the precipitation of coarse lamellar discontinuousβ-Cu_(4)Ti precipitates along the grain boundaries,resulting in Cu-Ti alloys with high yield strength and good electrical *** results showed that the continuous precipitation ofβ'-Cu_(4)Ti was accelerated by the Mg additions,which reduced the supersaturation of the matrix,thereby reducing the chemical driving force for the discontinuous *** the other hand,Mg additions increased the mismatch between the discontinuousβ-Cu_(4)Ti precipitates and matrix decreased the nucleation rate of the discontinuous precipitates,and increased the spacing of the discontinuous precipitation layer,resulting in a lower growth rate of the discontinuous ***,the addition of Mg to Cu-Ti alloys enhances the strength and improves the resistance to over-ageing.

关键词： Cu-Ti-Mg alloy Precipitation hardening Discontinuous precipitation Continuous precipitation Microstructure formation mechanism

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Effect of slow shot speed on externally solidified crystal,porosity and tensile property in a newly developed high-pressure die-cast Al-Si alloy

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China Foundry 2024年第1期21卷 11-19页

作者： wen-ning Liu Wei Zhang Peng-yue Wang Yi-xian Liu Xiang-yi Jiao Ao-xiang Wan cheng-gang Wang Guo-dong Tong Shou-mei Xiong School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China Key Laboratory for Advanced Materials Processing Technology Tsinghua UniversityBeijing 100084Beijing China FAW Group Co. Ltd.Changchun 130013China China FAW Foundry Co. Ltd.Changchun 130013China

The effect of slow shot speed on externally solidified crystal(ESC),porosity and tensile property in a newly developed high-pressure die-cast Al-Si alloy was investigated by optical microscopy(OM),scanning electron microscopy(SEM)and laboratory computed tomography(CT).Results showed that the newly developed AlSi9MnMoV alloy exhibited improved mechanical properties when compared to the AlSi10MnMg *** AlSi9MnMoV alloy,which was designed with trace multicomponent additions,displays a notable grain refining effect in comparison to the AlSi10MnMg *** elements Ti,Zr,V,Nb,B promote heterogeneous nucleation and reduce the grain size of primaryα-*** a lower slow shot speed,the large ESCs are easier to form and gather,developing into the dendrite net and *** an increase in slow shot speed,the size and number of ESCs and porosities significantly *** addition,the distribution of ESCs is more dispersed and the net-shrinkage *** tensile property is greatly improved by adopting a higher slow shot *** ultimate tensile strength is enhanced from 260.31 MPa to 290.31 MPa(increased by 11.52%),and the elongation is enhanced from 3.72%to 6.34%(increased by 70.52%).

关键词： hypoeutectic Al-Si alloy high pressure die casting porosity externally solidified crystal tensile property

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Microstructures and mechanical properties of laser-directed energy deposited CrCoNi medium-entropy alloy

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Rare Metals 2024年第7期43卷 3286-3300页

作者： wen-Jie Zhao Chang-Yu Liu Peng-cheng Che Zhi-Liang Ning Hong-Bo Fan Jian-Fei Sun Yong-Jiang Huang Alfonso H.W.Ngan National Key Laboratory for Precision Hot Processing of Metals Harbin Institute of TechnologyHarbin 150001China Space Environment Simulation Research Infrastructure Harbin Institute of TechnologyHarbin 150001China Department of Mechanical Engineering The University of Hong KongHong Kong 999077China

The distinctive intrinsic heat treatment(IHT)originating from cyclic reheating in the laser-directed energy deposition(LDED) has attracted growing attention in recent *** this investigation,simulations and experimental characterizations were performed to examine the impact of IHT on the micros true ture and mechanical properties of LDED-fabricated CrCoNi medium-entropy alloy(MEA).The results show that the intensity of the IHT is proportional to the utilized laser energy density(LED).As the LED increased,significant dynamic recrystallization and grain refinement occurred within the alloy due to the enhanced intensity of ***,the high LED leads to severe hot cracking within the as-built MEA,resulting in inferior *** decreasing LED,the hot cracking was effectively ***,low LED weakened the intensity of IHT and consequently inhibited kinetic conditions of dynamic recrystallization,resulting in a heterogeneous grain structure characterized by multi-scale-sized *** structure provides significant hetero-deformation-induced hardening during plastic deformation,enabling the alloy to have a sustainable work-hardening *** expect that this work will have implications in taking full advantage of the unique IHT of the LDED process to fabricate ME As with excellent metallurgical quality and mechanical performance.

关键词： Intrinsic heat treatment Laser-directed energy deposition CrCoNi MEA Dynamic recrystallization Heterogeneous grain structure

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Cyclization mechanism of monoterpenes catalyzed by monoterpene synthases in dipterocarpaceae

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Synthetic and Systems Biotechnology 2024年第1期9卷 11-18页

作者： Xiaoyun Lu Jie Bai Zunzhe Tian Congyu Li Nida Ahmed Xiaonan Liu Jian cheng Lina Lu Jing Cai Huifeng Jiang wen Wang School of Ecology and Environment Northwestern Polytechnical UniversityXi’anShanxi710072China Key Laboratory of Engineering Biology for Low-Carbon Manufacturing Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin300308China

Monoterpenoids are typically present in the secretory tissues of higher plants,and their biosynthesis is catalyzed by the action of monoterpene synthases(MTSs).However,the knowledge about these enzymes is restricted in a few plant *** are responsible for the complex cyclization of monoterpene precursors,resulting in the production of diverse monoterpene *** enzymatic reactions are considered exceptionally complex in ***,it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid *** our study,we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene *** focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic,monocyclic and bicyclic products in MTSs,we observed that even a single amino acid mutation can change the specificity and diversity of MTS products,which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation ***,residues N340,I448,and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene *** in these residues,either directly or indirectly,can impact the synthesis of single monoterpenes or their *** revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs,it will be possible to reasonably design and engineer different catalytic activities into existing MTSs,laying a foundation for the artificial design and industrial application of MTSs.

关键词： Cyclization Monoterpene synthases Intermediate stabilization

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