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Synthetic and Systems Biotechnology 2018年第1期3卷 56-63页

作者： Paul N.Schwarz Luisa Roller Andreas Kulik Wolfgang Wohlleben evi stegmann Microbiology/Biotechnology Interfaculty Institute of Microbiology and Infection Medicine Tübingen(IMIT)Eberhard Karls University TübingenTübingenGermany German Centre for Infection Research(DZIF) Partner Site TübingenTübingenGermany

The isoprenoid brasilicardin A is a promising immunosuppressant compound with a unique mode of action,high potency and reduced toxicity compared to today's standard ***,production of brasilicardin has been hampered since the producer strain Nocardia terpenica IFM0406 synthesizes brasilicardin in only low amounts and is a biosafety level 2 ***,we were able to heterologously express the brasilicardin gene cluster in the nocardioform actinomycete Amycolatopsis *** brasilicardin congeners,intermediates of the BraA biosynthesis,were *** chemical synthesis of the brasilicardin core structure has remained elusive we intended to produce high amounts of the brasilicardin backbone for semi synthesis and ***,we used a metabolic engineering approach to increase heterologous production of brasilicardin in *** heterologous expression of genes encoding the MVA pathway and expression of diterpenoid specific prenyltransferases were used to increase the provision of the isoprenoid precursor isopentenyl diphosphate(IPP)and to channel the precursor into the direction of diterpenoid *** approaches contributed to an elevated heterologous production of the brasilicardin backbone,which can now be used as a starting point for semi synthesis of new brasilicardin congeners with better properties.

关键词： Norcardia terpenica IFM0406 Mevalonate pathway Isoprenoids Prenyltransferases

G protein-mediated signal transduction: a molecular choreography of G protein activation after GTP binding

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3155-3157页

作者： evi Kostenis Lars Jurgenliemke Judith Alenfelder Department of Molecular- Cellular-and PharmacobiologyInstitute of Pharmaceutical BiologyUniversity of BonnBonnGermany Graduate Training Group RTG2873 University of BonnBonnGermany

A recent report from the Skiniotis group,'published in Nature,provides fascinating insight into the molecular choreography underlying a quintessential cellular signaling mechanism:G protein-mediated signal *** time-resolved cryo-EM,the authors pieced together many sequential structural snapshots to visualize how a trimeric aβy G protein-after being convinced by its activated G protein-coupled receptor(GPCR)to release GDP-picks up GTP,to set in motion finely tuned conformational transitions that lead to the conversion into the active state and,finally,subunit dissociation as well as disengagement from the receptor.

关键词： Skin activation finally

Health awareness and lifestyle toward healthcare-seeking behavior among students in Universitas Advent Indonesia

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Frontiers of Nursing 2024年第3期11卷 337-342页

作者： Alvin Salim Natasha Ulima Sianturi evi Martha Suryani Yunus Elon Nursing Department Riau Andalan Pulp&PaperRiauIndonesia Faculty of Nursing Binawan UniversityJakartaIndonesia Nursing Department UNAI ClinicBandungIndonesia Faculty of Nursing Universitas Advent IndonesiaBandungIndonesia

Objective:Healthcare-seeking behavior(HSB)would affect the prevalence of morbidity and *** are various factors that affect one's *** study aimed to determine if health awareness and lifestyle might relate to ***:A cross-sectional study was applied by using three questionnaires to determine par ticipants'health awareness,lifestyle,and *** study took place in Universitas Advent Indonesia and the students were recruited to be par ***:There were 39 par ticipants joined in this *** of the par ticipants were females,third-year students,and from Accounting *** all participants were aware of their low risk of health issues,had a fine lifestyle,and had moderate ***:One's urge to seek health care facilities was not related to their health awareness and *** was no fur ther study to contradict with this finding at this moment.

关键词： health awareness healthcare-seeking behavior healthcare service utilization lifestyle public health

Elevated fluid and glycosaminoglycan content in the Achilles tendon contribute to higher intratendinous pressures:Implications for Achilles tendinopathy

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Journal of Sport and Health Science 2024年第6期13卷 863-871页

作者： Lauren Pringels Gert-Jan Van Valckenborgh Patrick Segers Amelie Chevalier Hedwig Stepman evi Wezenbeek Arne Burssens Luc Vanden Bossche Department of Physical and Rehabilitation Medicine Ghent University HospitalGhent 9000Belgium Department of Rehabilitation Sciences and Physiotherapy Ghent UniversityGhent 9000Belgium Department of Electronics and Information Systems Ghent UniversityGhent 9000Belgium Department of Electromechanics University of AntwerpAntwerp 2020Belgium Department of Laboratory Medicine Ghent University HospitalGhent 9000Belgium Department of Orthopedic Surgery Ghent University HospitalGhent 9000Belgium

Background:Tendinopathy alters the compositional properties of the Achilles tendon by increasing fluid and glycosaminoglycan *** has been speculated that these changes may affect intratendinous pressure,but the extent of this relationship remains ***,we aimed to investigate the impact of elevated fluid and glycosaminoglycan content on Achilles tendon intratendinous pressure and to determine whether hyaluronidase(HYAL) therapy can intervene in this potential ***:Twenty paired fresh-frozen cadaveric Achilles tendons were mounted in a tensile-testing machine and loaded up to 5% *** resting(at 0% strain) and dynamic pressure(at 5% strain) were assessed using the microcapillary infusion ***,intratendinous pressure was measured under native conditions before and after infusion of 2 mL physiological ***,80 mg of glycosaminoglycans were administered bilaterally to the paired *** right tendons were additionally treated with 1500 units of ***,both groups were retested,and the glycosaminoglycan content was ***:It was found that both elevated fluid and glycosaminoglycan content resulted in higher intratendinous resting and dynamic pressures(p <0.001).HYAL treatment induced a 2.3-fold reduction in glycosaminoglycan content(p=0.002) and restored intratendinous ***:The results of this study demonstrated that elevated fluid and glycosaminoglycan content in Achilles tendinopathy contribute to increased intratendinous re sting and dynamic pressures,which can be explained by the associated increased volume and reduced permeability of the tendon matrix,*** degrades glycosaminoglycans sufficiently to lower intratendinous pressures and may,therefore,serve as a promising treatment.

关键词： Achilles tendon Achilles tendinopathy Intratendinous pressure Glycosaminoglycans Tendon fluid

Formulating Dead Sea Mud in Cosmetic Products, Its Effects on Skin, and the Underlying Biological Mechanism: A Review

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第3期14卷 276-288页

作者： Ze’evi Ma’or Dror Cohen Assaf Assis Dead Sea Hub Fosun Jinmei Cosmetics Dead Sea Israel Laboratory of Biochemistry and Biotechnology of the Skin The Dead Sea & Arava Science Center Masada Israel Ahava Dead Sea Laboratories Ltd. Dead Sea Israel

Research Background: The marketing of cosmetic products derived from Dead Sea (DS) mud has undergone significant evolution, transforming from simple souvenirs into a large-scale cosmetic industry offering a diverse array of products. DS mud is utilized both as pure mud for home spa treatments and as an active ingredient in cosmetic and cosmeceutical formulations. Its global appeal is largely due to its natural, health-oriented image, which aligns with consumer preferences and provides assurance regarding its use in skincare. Research Objectives: This review examines the published data related to the rationale for formulating DS mud in cosmetics, the biological and cosmetic effects of DS mud on the skin, and the speculated bio-mechanisms underlying these effects. Methods: We screened relevant literature on DS mud collected from the shores of the Dead Sea in Jordan and Israel. Publications on mineral muds excavated in different locations around the globe, as well as studies on the biological mechanisms of other DS minerals, were also reviewed as indications and supportive recommendations. Summarizing the vast collected data into a comprehensive review was undertaken to expose readers to the various aspects of DS mud in cosmetics. Results: The primary reason for formulating DS mud in skincare products is its deep cleansing and skin detoxification properties. Consequently, it is often incorporated into rinse-off masks, soaps, and scrubbing products. Additionally, DS mud is used in leave-on products and sheet masks. Cosmeceutical applications of DS mud, recommended for various skin conditions, offer complementary treatments to improve the quality of life for people with skin diseases. The physicochemical and biological effects of DS mud are driven by its rich mineral ion composition, including magnesium, calcium, sodium, potassium, zinc, and strontium—elements known to improve skin barrier function, enhance hydration, and reduce inflammation. The high salt concentration

关键词： Dead Sea Mineral Cosmetics Mud Health

Functional Dependence of IM and HV Angle in Hallux Valgus Deformity before and after Operative

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Journal of Applied Mathematics and Physics 2024年第5期12卷 1626-1646页

作者： Nenad Stojanović Mirko Sovilj Vesna Ivanišević Department of Mathematics Faculty of Philosophy University of Banja Luka Banja Luka Bosnia and Herzegovina Higher Medical School Prijedor Bosnia and Herzegovina Faculty of Medicine University of Banja Luka Banja Luka Bosnia and Hercegovina

Hallux valgus is a relatively common and multifaceted complex deformity of the front part of the foot. It is the result of multiple effects of innate (endogenous) and exogenous etiological factors with different degrees of influence. The degree of hallux valgus deformity is usually assessed by radiological values of hallux valgus (HV) and intermetatarsal (IM) angles. The aim of the paper is to justify the definition of hallux valgus deformity as a function of one angle, (HVA or IMA), and then to determine the functional connection and the most suitable function equalizing the values of the angles IMA and HVA. As hallux valgus is a double angulation deformity, the analytically determined connection between the HVA and IMA angles reduces the study of the deformity to the study of function with one argument, and makes the analysis of deformity changes before and after operative treatment simpler. For the determined connections between the angles, the values of linear proportionality coefficients and regression coefficients of corresponding linear functions of analytical equalization of the value of the IM angle and the degree of deformity for a given value of the HV angle were experimentally determined. The obtained results were checked on a sample of 396 operatively treated hallux valgus deformities. The presented analytical approach and the obtained functional links of IMA and HVA enable quantitative observation of the change in the degree of deformity based on the radiologically determined value of these angles, and the established nonlinear function will be useful for evaluating the expected value of the IM angle and the degree of deformity based only on the measured value of the HV angle. .

关键词： Functional Connection of Deformity Angles Analytical Equalization of IM Angle Values Hallux Valgus Intermetatarsal Angle Correction of Deformity

Potential of contemporary earth-sheltered buildings to achieve Plus Energy status in various European climates during the heating season

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Building Simulation 2024年第1期17卷 41-52页

作者： Aleksandar Nesovic Nebojsa Jurisevic Robert Kowalik lvana Terzic Faculty of Engineering University of KragujevacSestre Janjic 634000 KragujevacSerbia Faculty of Environmental Geomatic and Energy EngineeringKielce University of TechnologyTysigclecia Panstwa Polskiego725-314 KielcePoland

This study investigates the potential of contemporary Earth-Sheltered Buildings to contribute to sustainable societies by achieving Plus Energy Building status during the heating *** buildings analyzed are intended to house a four-member family(102.5 m^(2)).The house is equipped with a ground source heat pump,geothermal vertical probes,floor heating panels,an energy recovery ventilator,and building-integrated photovoltaic panels installed on the exposed building *** numerical analysis(using EnergyPlus software)was carried out for nine European sites covering five different climatic zones(namely:southern,Atlantic,continental,alpine,and northern climate)and three latitude belts spanning Europe from south to *** above 65°N(northern and alpine climate)could not achieve Plus Energy status with 20% efficient *** 15% efficient BIPVs,the building above 59°N(northern climate)was incapable of achieving this as *** the monthly time step,the buildings in the southern and Atlantic climates with 15% efficient BiPVs were able to produce an energy surplus every month,as was the building in theAlps with 20% efficientBIPVs.

关键词： civil engineering earth-sheltered buildings renewable energy sustainable societies Plus Energy Buildings Energy Plus software

Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

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Oncology Research 2024年第5期32卷 807-815页

作者： MARKO SKELIN BRUNA PERKOV-STIPIČIN SANJA VUŠKOVIĆ MARINAŠANDRK PLEHAČEK ANE BAŠIĆ DAVIDŠARČeviĆ MAJA ILIĆ IVAN KREČAK Pharmacy Department General Hospital ofŠibenik-Knin CountyŠibenikCroatia Faculty of Medicine University of RijekaRijekaCroatia Undergraduate Study in Nursing University of Applied SciencesŠibenikCroatia Department of Oncology University Hospital Center ZagrebZagrebCroatia Pharmacies Joukhadar Sveta NedeljaCroatia Pharmacies Prima Pharme ZagrebCroatia Pharmacy Department General Hospital ZadarZadarCroatia Pharmacy Department General Hospital PulaPulaCroatia Department of Internal Medicine General Hospital ofŠibenik-Knin CountyŠibenikCroatia

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)***,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically *** study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer ***:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each *** examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer ***:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR ***,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous *** proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current *** the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)*** variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer ***:One-third of the current ESMO CPG recommendations are supported by the highest level of *** well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

关键词： ESMO guidelines Clinical practice guidelines Level of evidence Grade of recommendation

In vivo femtosecond laser nanosurgery of the cell wall enabling patch-clamp measurements on filamentous fungi

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Microsystems & Nanoengineering 2024年第2期10卷 251-267页

作者： Tanja Pajić Katarina Stevanović Nataša V.Todorović Aleksandar J.Krmpot Miroslav Živić Svetlana Savić-Šević Steva M.Lević Marina Stanić Dejan Pantelić Brana Jelenković Mihailo D.Rabasović Institute of Physiology and Biochemistry“Ivan Djaja” Faculty of BiologyUniversity of BelgradeStudentski trg 1611158BelgradeSerbia Institute for Biological Research“Siniša Stanković” University of BelgradeNational Institute of the Republic of SerbiaBulevar Despota Stefana 14211000BelgradeSerbia Institute of Physics Belgrade University of BelgradeNational Institute of the Republic of SerbiaPregrevica 11811080BelgradeSerbia University of Belgrade Faculty of AgricultureNemanjina Street 611080BelgradeSerbia Institute for Multidisciplinary Research University of BelgradeKneza Višeslava 111030BelgradeSerbia

Studying the membrane physiology of filamentous fungi is key to understanding their interactions with the environment and crucial for developing new therapeutic strategies for disease-causing ***,their plasma membrane has been inaccessible for a micron-sized patch-clamp pipette for pA current recordings due to the rigid chitinous cell ***,we report the first femtosecond IR laser nanosurgery of the cell wall of the filamentous fungi,which enabled patch-clamp measurements on protoplasts released from hyphae.A reproducible and highly precise(diffraction-limited,submicron resolution)method for obtaining viable released protoplasts was *** release from the nanosurgery-generated incisions in the cell wall was achieved from different regions of the *** plasma membrane of the obtained protoplasts formed tight and high-resistance(GΩ)contacts with the recording *** entire nanosurgical procedure followed by the patch-clamp technique could be completed in less than 1 *** to previous studies using heterologously expressed channels,this technique provides the opportunity to identify new ionic currents and to study the properties of the ion channels in the protoplasts of filamentous fungi in their native environment.

关键词： patch recording laser

Biological characteristics and clinical management of uveal and conjunctival melanoma

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Oncology Research 2024年第8期32卷 1265-1285页

作者： SNJEŽANA KAŠTELAN ANA DIDOVIĆPAVIČIĆ DARIA PAŠALIĆ TAMARA NIKUŠEVA-MARTIĆ SAMIRČANOVIĆ PETRA KOVAČeviĆ SUZANA KONJEVODA School of Medicine University of ZagrebZagreb10000Croatia Department of Ophthalmology Clinical Hospital DubravaZagreb10000Croatia Department of Ophthalmology Zadar General HospitalZadar23000Croatia Department of Medical Chemistry Biochemistry and Clinical ChemistrySchool of MedicineUniversity of ZagrebZagreb10000Croatia Department of Biology and Genetics School of MedicineUniversity of ZagrebZagreb10000Croatia School of Medicine University of SplitSplit21000Croatia Department of Health Studies University of ZadarZadar23000Croatia

Uveal and conjunctival melanomas are relatively rare tumors;nonetheless,they pose a signiﬁcant risk of mortality for a large number of affected *** pathogenesis of melanoma at different sites is very similar,however,the prognosis for patients with ocular melanoma remains unfavourable,primarily due to its distinctive genetic proﬁle and tumor *** of considerable advances in understanding the genetic characteristics and biological behaviour,the treatment of uveal and conjunctival melanoma remains a formidable *** enhance the prospect of success,collaborative efforts involving medical professionals and researchers in theﬁelds of ocular biology and oncology are *** data show a lack of well-designed randomized clinical trials and limited beneﬁts in current forms of treatment for these *** advancements in the development of effective melanoma therapeutic strategies,all current treatments for uveal melanoma(UM)and conjunctival melanoma(CoM)remain unsatisfactory,resulting in a poor long-term *** trials offer hope for positive outcomes in advanced and metastatic tumors.A more comprehensive understanding of the genetic and molecular abnormalities involved in the development and progression of ocular melanomas opens the way for the development of personalized therapy,with various potential therapeutic targets currently under *** comprehension of the molecular pathogenesis of UM and CoM and their speciﬁcities may aid in the development of new and more effective systemic therapeutic agents,with the hope of improving the prognosis for patients with metastatic disease.

关键词： Uveal melanoma Conjunctival melanoma Genetic characteristics Immune checkpoint inhibitors Target molecular inhibitors