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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar hyun Joon kim Deok Ryong kim Department of Biochemistry and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

Depolarization mitigated in ferroelectric Hf_(0.5)Zr_(0.5)O_(2)ultrathin films(<5 nm)on Si substrate by interface engineering

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Journal of Advanced Ceramics 2024年第3期13卷 282-292页

作者： Se hyun kim Younghwan Lee Dong hyun Lee Geun Hyeong Park hyun Woo Jeong Kun Yang Yong Hyeon Cho Young Yong kim Min Hyuk Park Department of Materials Science and Engineering College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Research Institute of Advanced Materials College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Inter-university Semiconductor Research Center College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Pohang Accelerator Laboratory Pohang University of Science&TechnologyPohang 790784Republic of Korea

(Hf,Zr)O_(2)offers considerable potential for next-generation semiconductor devices owing to its nonvolatile spontaneous polarization at the ***,scaling this material to sub-5 nm thickness poses several challenges,including the formation of an interfacial layer and high trap *** particular,a low-k SiO_(2)interfacial layer is naturally formed when(Hf,Zr)O_(2)films are directly grown on a Si substrate,leading to high depolarization fields and rapid reduction of the remanent *** address these issues,we conducted a study to significantly improve ferroelectricity and switching endurance of(Hf,Zr)O_(2)films with sub-5 nm thicknesses by inserting a TiO_(2)interfacial *** deposition of a Ti film prior to Hf_(0.5)Zr_(0.5)O_(2)film deposition resulted in a high-k TiO_(2)interfacial layer and prevented the direct contact of Hf_(0.5)Zr_(0.5)O_(2)with *** findings show that the high-k TiO_(2)interfacial layer can reduce the SiO_(2)/Si interface trap density and the depolarization field,resulting in a switchable polarization of 60.2μC/cm^(2)for a 5 nm thick Hf_(0.5)Zr_(0.5)O_(2)***,we propose that inserting a high-k TiO_(2)interfacial layer between the Hf_(0.5)Zr_(0.5)O_(2)film and the Si substrate may offer a promising solution to enhancing the ferroelectricity and reliability of(Hf,Zr)O_(2)grown on the Si substrate and can pave the way for next-generation semiconductor devices with improved performance.

关键词： ferroelectric charge trapping hafnia depolarization

Fabrication of heteroatom-doped cobalt oxide yolk–shell microsphere using recycled solution from waste materials and their excellent electrochemical properties as an anode material for lithium-ion batteries

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Rare Metals 2024年第10期43卷 4934-4947页

作者： Yeong Beom kim Chanho kim Seung-hyun kim Yun Chan Kang Dongju Lee Gi Dae Park Department of Advanced Materials Engineering Chungbuk National University Department of Materials Science and Engineering Korea University Research Institute YKSintering Co.Ltd.

Heteroatom-doped transition metal oxides have attracted great attention as advanced anode materials for lithium-ion batteries due to their high theoretical capacity and superior ***,the limited resource availability has led to a substantial rise in prices for valuable metals such as Ni and Co,posing a significant challenge for their *** address this issue,recycling of these metals from waste materials have gained prominence,and particularly the recovery of Co has been mostly focused on its economic ***,we introduced a novel recycling strategy for fabrication of heteroatomdoped CoOx（comprising mainly Co3O4with a minor CoO phase） anode with a yolk–shell structure for lithium-ion batteries,by separating Co from cemented tungsten carbide *** employing a simple leaching process and subsequent spray pyrolysis,the yolk–shell structured microsphere comprising CoOxwas successfully ***,the presence of other waste metals in the leachate facilitated multi-heteroatom doping during ***,the introduction of various dopants into CoOxinduced oxygen vacancy formation,thereby enhancing the electrochemical properties of the *** a result,compared with the phase-pure （undoped） CoOxyolk–shell,the heteroatom-doped CoOxyolk–shell exhibited robust cycling stability (602 mAh·g-1for 200 cycles at 1 A·g-1) and excellent rate capability(210 mAh·g-1at 10 A·g-1).

关键词： Anode Cobalt oxide Heteroatom doping Lithium-ion batteries Recycling

Increasing concentrations of dietary threonine,tryptophan,and glycine improve growth performance and intestinal health with decreasing stress responses in broiler chickens raised under multiple stress conditions

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Animal Nutrition 2024年第3期18卷 145-153页

作者： hyun Woo kim Jong Hyuk kim Gi Ppeum Han Dong Yong Kil Department of Animal Science and Technology Chung-Ang UniversityAnseong-siGyeonggi-do 17546Republic of Korea Department of Animal Science Chungbuk National UniversityCheongju 28644Republic of Korea

The current study aimed to compare the effects of increasing concentrations of dietary threonine(Thr),tryptophan(Trp),and glycine(Gly)on growth performance,stress biomarkers,and intestinal function in broiler chickens under multiple stress *** hundred sixty broiler chickens at 21 d old were randomly allotted to 5 treatments with 8 *** in a positive control(PC)treatment were raised under low stock density(16.9 birds/m2 per cage)with recommended environmental conditions,whereas birds in 4 treatments were subjected to multiple stress conditions:a cyclic heat stress of 30±0.3°C for 10 h and 23±0.2°C for 14 h per day with high stock density(25.3 birds/m2 per cage).A basal diet was assigned to both PC and negative control(NC)*** additional diets were individually formulated to contain double concentrations of digestible Thr,Trp,or Gly+Ser compared with their concentrations in the basal *** experiment lasted for 14 *** showed that NC treatment had less growth performance(P<0.001),jejunal goblet cell counts(P=0.018),and trans-epithelial electrical resistance(TEER;P<0.001),but greater(P=0.026)feather corticosterone(CORT)concentrations than PC *** treatment showed the least(P<0.001)feed conversion ratio(FCR)among treatments under multiple stress ***,Trp,and Gly treatments had less(P=0.026)feather CORT concentrations,but had greater(P<0.001)TEER than NC *** conclusion,increasing concentrations of dietary Thr,Trp,or Gly improve the growth performance and intestinal health in broiler chickens with decreasing stress response under multiple stress conditions.

关键词： Broiler chicken Glycine Multiple stress Threonine Tryptophan

Metabolic relationships between marine red algae and algae‑associated bacteria

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Marine Life Science & Technology 2024年第2期6卷 298-314页

作者： Kyung hyun kim Jeong Min kim Ju Hye Baek Sang Eun Jeong Hocheol kim Hwan Su Yoon Che Ok Jeon Department of Biological Sciences and Biotechnology Hannam UniversityDaejon 34054Republic of Korea Department of Life Science Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biological Sciences Sungkyunkwan UniversitySuwon 16419Republic of Korea

Mutualistic interactions between marine phototrophs and associated bacteria are an important strategy for their success-ful survival in the ocean,but little is known about their metabolic ***,bacterial communities in the algal sphere(AS)and bulk solution(BS)of nine marine red algal cultures were analyzed,and Roseibium and Phycisphaera were identified significantly more abundantly in AS than in *** metabolic features of Roseibium RMAR6-6(isolated and genome-sequenced),Phycisphaera MAG 12(obtained by metagenomic sequencing),and a marine red alga,Porphyridium purpureum CCMP1328(from GenBank),were analyzed ***6-6 has the genetic capability to fix nitrogen and produce B vitamins(B1,B2,B5,B6,B9,and B12),bacterioferritin,dimethylsulfoniopropionate(DMSP),and phenylacetate that may enhance algal growth,whereas MAG 12 may have a limited metabolic capability,not producing vitamins B9 and B12,DMSP,phenylacetate,and siderophores,but with the ability to produce bacitracin,possibly modulating algal *** CCMP1328 lacks the genetic capability to fix nitrogen and produce vitamin B12,DMSP,phenylacetate,and *** was shown that the nitrogen-fixing ability of RMAR6-6 promoted the growth of ***-pureum,and DMSP reduced the oxidative stress of *** metabolic interactions between strain RMAR6-6 and *** CCMP1328 were also investigated by the transcriptomic analyses of their monoculture and *** together,potential metabolic relationships between Roseibium and *** were *** study provides a bet-ter understanding of the metabolic relationships between marine algae and algae-associated bacteria for successful growth.

关键词： Metabolic relationship Marine red algae Symbiotic bacteria Roseibium Phycisphaera Porphyridium

Chemical and mechanical properties of stainless, environment-friendly, and nonflammable Mg alloys (SEN alloys): A review

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Journal of Magnesium and Alloys 2024年第3期12卷 841-872页

作者： Jong Un Lee hyun Ji kim Sang-Cheol Jin Ye Jin kim Young Min kim Bong Sun You Jun Ho Bae Sung Hyuk Park Advanced Metals Division Korea Institute of Materials ScienceChangwon 51508Republic of Korea Department of Materials Science and Metallurgical Engineering Kyungpook National UniversityDaegu 41566Republic of Korea Missile Research Institute Agency for Defense DevelopmentDaejeon 34060Republic of Korea

This review article provides overall understanding of stainless,environment-friendly,and nonflammable Mg alloys(SEN alloys)recently developed at the Korea Institute of Materials *** alloys are produced by adding small amounts of Ca and Y(each<1 wt%)into commercial Mg–Al based alloys,resulting in exceptional ignition and corrosion resistances and impressive mechanical *** main advantages of SEN alloys are as follows.(1)A dense multi-oxide layer of SEN alloys comprising MgO,CaO,and Y_(2)O_(3) impedes the outward dispersion of Mg vapor and the inward penetration of O_(2) during oxidation,thereby enhancing the oxidation and ignition resistances.(2)The presence of Ca-and Y-based second-phase particles in SEN alloys can enhance their corrosion resistance because Ca-containing particles prevent the spread of corrosion,and the replacement of Al-containing particles with less noble ones containing Y(e.g.,Al–Mn–Y or Al–Y particles)retards corrosion.(3)The addition of minor amounts of Ca and Y renders excellent mechanical properties due to improved strengthening *** enhanced properties are attributed to more pronounced dynamic recrystallization and grain refining behaviors caused by the second-phase particles during extrusion.(4)Despite the presence of various types of second-phase particles,the fatigue properties of SEN9 alloys are similar to those of commercial AZ91 alloys.(5)Simultaneous introduction of Ca and Y suppresses the formation of Mg17Al12 discontinuous precipitates during aging,leading to the enhanced elongation of aged SEN alloys.(6)Adding mischmetal into the SEN9 alloy leads to a six-fold enhancement in ***,the studies conducted on SEN alloys demonstrate their excellent ignition and corrosion resistances and mechanical properties,which broaden the industrial applications of Mg alloys by addressing their inherent weaknesses.

关键词： SEN magnesium alloy Corrosion resistance Ignition resistance Mechanical properties Extrudability.

Stable immobilization of lithium polysulfides using three-dimensional ordered mesoporous Mn_(2)O_(3) as the host material in lithium-sulfur batteries

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Carbon Energy 2024年第6期6卷 99-112页

作者： Sung Joon Park Yun Jeong Choi hyun-seung kim Min Joo Hong Hongjun Chang Janghyuk Moon Young-Jun kim Junyoung Mun Ki Jae kim Department of Energy Science Sungkyunkwan UniversitySuwonGyeonggi-doRepublic of Korea Department of Energy Engineering Konkuk UniversitySeoulRepublic of Korea Advanced Batteries Research Center Korea Electronic Technology InstituteSeongnamRepublic of Korea Department of Future Energy Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Department of Energy Systems Engineering Chung-Ang UniversitySeoulRepublic of Korea SKKU Advanced Institute of Nanotechnology Sungkyunkwan UniversitySuwonGyeonggi-doRepublic of Korea SKKU Institute of Energy Science and Technology(SIEST) Sungkyunkwan UniversitySuwonRepublic of Korea School of Advanced Materials Science and Engineering Sungkyunkwan UniversitySuwonRepublic of Korea

Lithium-sulfur batteries(LSBs)have drawn significant attention owing to their high theoretical discharge capacity and energy ***,the dissolution of long-chain polysulfides into the electrolyte during the charge and discharge process(“shuttle effect”)results in fast capacity fading and inferior electrochemical *** this study,Mn_(2)O_(3)with an ordered mesoporous structure(OM-Mn_(2)O_(3))was designed as a cathode host for LSBs via KIT-6 hard templating,to effectively inhibit the polysulfide shuttle ***-Mn_(2)O_(3)offers numerous pores to confine sulfur and tightly anchor the dissolved polysulfides through the combined effects of strong polar-polar interactions,polysulfides,and sulfur chain *** OM-Mn_(2)O_(3)/S composite electrode delivered a discharge capacity of 561 mAh g^(-1) after 250 cycles at 0.5 C owing to the excellent performance of OM-Mn_(2)O_(3).Furthermore,it retained a discharge capacity of 628mA h g^(-1) even at a rate of 2 C,which was significantly higher than that of a pristine sulfur electrode(206mA h g^(-1)).These findings provide a prospective strategy for designing cathode materials for high-performance LSBs.

关键词： host material lithium-sulfur battery ordered mesoporous structure shuttle effect transition-metal oxides

Effect of Meteorological Data Assimilation on Regional Air Quality Forecasts over the Korean Peninsula

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Journal of Meteorological Research 2024年第2期38卷 262-284页

作者： Yunjae CHO hyun Mee kim Eun-Gyeong YANG Yonghee LEE Jae-Bum LEE Soyoung HA Department of Atmospheric Sciences Yonsei UniversitySeoul 03722Republic of Korea Air Quality Forecasting Center National Institute of Environmental ResearchIncheon 22689Republic of Korea National Center for Atmospheric Research BoulderCO 80305USA University of Maryland Baltimore County BaltimoreMD 21250USA Global Modeling and Assimilation Office NASA Goddard Space Flight CenterGreenbeltMD 20771USA

The Weather Research and Forecasting model coupled with Chemistry(WRF-Chem),a type of online coupled chemistry-meteorology model(CCMM),considers the interaction between air quality and meteorology to improve air quality *** data assimilation(DA)can be used to reduce uncertainty in meteorological field,which is one factor causing prediction uncertainty in the *** this study,WRF-Chem and three-dimensional variational DA were used to examine the impact of meteorological DA on air quality and meteorological forecasts over the Korean *** nesting model domains were configured over East Asia(outer domain)and the Korean Peninsula(inner domain).Three experiments were conducted by using different DA domains to determine the optimal model domain for the meteorological *** the meteorological DA was performed in the outer domain or both the outer and inner domains,the root-mean-square error(RMSE),bias of the predicted particulate matter(PM)concentrations,and the RMSE of predicted meteorological variables against the observations were smaller than those in the experiment where the meteorological DA was performed only in the inner *** indicates that the improvement of the synoptic meteorological fields by DA in the outer domain enhanced the meteorological initial and boundary conditions for the inner domain,subsequently improving air quality and meteorological *** to the experiment without meteorological DA,the RMSE and bias of the meteorological and PM variables were smaller in the experiments with *** effect of meteorological DA on the improvement of PM predictions lasted for approximately 58-66 h,depending on the ***,the uncertainty reduction in the meteorological initial condition by the meteorological DA contributed to a reduction of the forecast errors of both meteorology and air quality.

关键词： meteorological data assimilation regional air quality forecast particulate matter concentration optimal model domain forecast error WRF-Chem

New anti-mesenteric delta-shaped stapled anastomosis: Technical report with short-term postoperative outcomes in patients with Crohn’s disease

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2592-2601页

作者： Jong Lyul Lee Yong Sik Yoon hyun Gu Lee Young Il kim Min hyun kim Chan Wook kim In Ja Park Seok-Byung Lim Chang Sik Yu Division of Colon and Rectal Surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea Department of Surgery Gangdong Kyung Hee University HospitalSeoul 05278South Korea

BACKGROUND Medical treatment for Crohn’s disease(CD)has continuously improved,which has led to a decrease in surgical recurrence *** these advancements,25%of patients will undergo repeat intestinal *** of CD com-monly occurs on the mesentery side of the anastomosis *** To compare the new anti-mesenteric side-to-side delta-shaped stapled anasto-mosis(DSA)with the conventional stapled functional end-to-end anastomosis(CSA).METHODS This retrospective study included CD patients who underwent ileo-ileal or ileo-colic anastomosis between January 2020 and December *** DSA technique employed a stapler to maintain the concept of anti-mesentery side-to-side ana-stomosis by performing a 90°vertical closure of the open window compared with the CSA *** the corner where the open window is closed,the DSA avoids forming a pouch and creates an anastomosis resembling a delta shape within the intestinal *** compared demographics,preoperative condition,operative findings,and operative outcomes for the two *** The study included 175 patients,including 92 in the DSA group and 83 in the CSA *** two groups were similar in baseline characteristics,preoperative medical treatment,and operative findings except for the Montreal classification *** 30-days postoperative complication rate was signi-ficantly lower in the DSA group compared with the CSA group(16.3%vs 32.5%,P=0.009).Ileus incidence was significantly lower in the DSA group than in the CSA group(4.3%vs 14.5%,P=0.033),and the hospital stay was shorter in the DSA group than in the CSA group(5.67±1.53 days vs 7.39±3.68 days,P=0.001).CONCLUSION The DSA technique was feasible and showed comparable postoperative outcomes with lower short-term complic-ations compared with the CSA *** studies on CD recurrence and long-term complications are warranted.

关键词： Crohn’s disease Surgery Anastomosis Complication Recurrence