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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

Platelet-rich plasma treatment for chronic wounds:A case report and literature review

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World Journal of Clinical Cases 2024年第33期12卷 6635-6643页

作者： ana Dimova Martin Boroš Stefan Dimov Janja Konjevod Maja Svetec Department of Surgery Zabok General Hospital and the Croatian Veterans HospitalZabok 49210Croatia Department of Surgery St Catherine Specialty HospitalZagreb 10000Croatia Department of Emergency Medicine Zabok General Hospital and the Croatian Veterans HospitalZabok 49210Croatia

BACKGROUND Wound healing is a complicated process that can be heavily influenced by patient comorbidities,in some cases leading to a chronic non-healing *** presented in the medical literature supporting the clinical use of autologous platelet-rich plasma(PRP)in treatment of such wounds is becoming increasingly *** involved include complex interactions between the patient’s thrombocytes,cytokines,and growth *** SUMMARY We present a case of a 72-year-old male patient with a long-standing chronic wound and multiple *** the course of more than 7 months,the patient was unsuccessfully treated with all routinely used measures,including different dressing *** antibiotic regimens were administered for wound infection,with repeated evaluation of microbiological swab ***,after three PRP applications,the wound showed clinical improvement with complete restitution of the epithelial layer of the *** PRP treatment may be beneficial to reduce healing time in chronic wounds.

关键词： Wound healing Platelet-rich plasma Growth factors Antibiotics Wound infection Case report

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

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World Journal of Cardiology 2024年第8期16卷 448-457页

作者： Petra GrubićRotkvić Luka Rotkvić anaĐuzelČokljat Maja Cigrovski Berković Department of Cardiology University Hospital Centre ZagrebZagreb 10000Croatia Department of Cardiology Magdalena Clinic for Cardiovascular DiseaseKrapinske Toplice 49217Croatia Department of internal Medicine General Hospital DubrovnikDubrovnik 20000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of *** previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic *** groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic *** To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body *** The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood *** evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMi)decrease,and lack of heart rate increase,linear regression analysis was *** There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of *** independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMi,while the predictor of stroke volume index increase was SGLT2i therapy *** SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic *** control contributes to the i

关键词： Sodium-dependent glucose transporter 2 inhibitors Dipeptidyl peptidase-4 inhibitors Type 2 diabetes mellitus Heart failure Diabetic cardiomyopathy Cardiovascular disease

转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化（英文）

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Engineering 2024年第1期 57-68页

作者： Vedrana Vi?i? Bo?kor Nika Foglar Goran Josipovi? Marija Klasi? ana Vuji? Branimir Plav?a Toma Keser Samira Smajlovi? Aleksandar Vojta Vlatka Zoldo? Laboratory for Epigenetics Department of Biology Faculty of Science University of Zagreb Genos Glycoscience Research Laboratory Faculty of Pharmacy and Biochemistry University of Zagreb

Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2) are key transcription factors that regulate a complex gene network in the liver,creating a regulatory transcriptional *** Encode and ChiP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase *** in silico analysis of HNF1A,HNF4A,and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the *** previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma ***,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan *** used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9(CRiSPR/dCas9) molecular tool for the downregulation of the HNF1A,HNF4A,and FOXA2 genes in HepG2 cells-a human liver cancer cell *** results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many gly co-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan *** effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantenna ry *** propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan *** also propose a model showing feedback loops with the mutual activation of HNF1A-FOXA2 and HNF4A-FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

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Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

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Oncology Research 2024年第8期32卷 1309-1322页

作者： ana S.CVETANOViC MATTEO LAMBERTiNi KEViN PUNiE GORana G.MATOViNA BRKO NiKOLA D.ZiVKOViC MAJA J.POPOViC MARiJana M.MiLOViC KOVACEViC LAZAR S.POPOViC Department for Oncology Medical Faculty NisUniversity of NisNis18000Serbia Clinic of Oncology University Clinical Centre NisNis18000Serbia Department of internal Medicine and Medical Sciences(DiMi) School of MedicineUniversity of GenovaGenova16100Italy Department of Medical Oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenova16100Italy Department of General Medical Oncology and Multidisciplinary Breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuven3001Belgium Department of Medical Oncology Oncology Institute of VojvodinaSremska Kamenica21208Serbia Department for Pathology Medical Faculty NisUniversity of NisNis18000Serbia Center for Pathology University Clinical Centre NisNis18000Serbia Faculty of Medicine University of Novi SadNovi Sad21000Serbia Department of Medical Oncology Institute of Oncology and Radiology SerbiaBelgrade11000Serbia

Oncofertility is an extremely signiﬁcant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but signiﬁcantly contributes to preserving life *** effect of chemotherapy can range from minimal effects to complete ovarian *** data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and *** ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufﬁciency(POi).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian ***,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POi have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological ***,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POi risk,regardless of the hormone receptor *** addition,studies on hematological malignancies have yielded negative results;nevertheless,theﬁndings must be interpreted with caution owing to numerous *** guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not *** this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisﬁeld

关键词： Gonadotropin-releasing hormone agonists(GnRHa) Fertility preservation Premature ovarian insufficiency(POi) Premenopausal patients

Study of the Conversion of Postconsumer Polystyrene on CeO₂/HZSM-5 Type Materials

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Journal of Materials Science and Chemical Engineering 2024年第4期12卷 29-41页

作者： Mirna Oliveira Sant’ana Anne Michelle Garrido Pedrosa Marcelo José Barros de Souza Graduate Program in Chemical Engineering at UFS Federal University of Sergipe (UFS) S&#227o Crist&#243v&#227o Brazil Department of Chemistry Federal University of Sergipe S&#227o Crist&#243v&#227o Brazil

The catalytic conversion of polystyrene (PS) was studied in the presence of the materials type HZSM-5, CeO2, 10% CeO2/HZSM-5 and 20% CeO2/HZSM-5, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and nitrogen adsorption at 77K. The catalytic tests were performed via thermogravimetric analysis (TG) at heating rates of 5, 10 and 20˚C min−1 in a temperature range from 30˚C to 900˚C. For the tests, a ratio of 30% by mass of each catalytic material mixed with PS was used and the activation energy of the degradation process was determined by the Vyazovkin method. The obtained results showed that the addition of the catalyst to the PS in general reduced its degradation temperature. The 10% CeO2/HZSM-5 catalyst showed greater efficiency, as it resulted in lower activation energy for PS degradation. Thus, the combination of CeO2 with HZSM-5 resulted in materials with potential for application in the catalytic degradation of polystyrene and the results indicate that the production of a composite material can be a good strategy to generate an increase in catalytic activity and a decrease in energy process activation.

关键词： HZSM-5 Zeolite Cerium Oxide Polystyrene Pyrolysis

Nutritional Screening Tools in institutionalized People: A Case Study of Using Nutritional Risk Screening (NRS 2002) and Mini Nutritional Assessment (MNA)

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Food and Nutrition Sciences 2024年第7期15卷 565-575页

作者： ana Cláudia Araújo Santana Daiane Costa dos Santos Mariana Buranelo Egea Campus Rio Verde Goiano Federal Institute of Education Science and Technology Rio Verde Brazil Centro Universitrio UniBRAS de Rio Verde Rio Verde Brazil

Nutritional status expresses the physiological and nutritional needs to maintain the composition and adequate functioning of the organism. NRS 2002 and MNA protocols were applied to short-term institutionalized patients in Rio Verde (Brazil). Older adults and people with special needs of all ages, both sexes, regardless of possible pathology they may have, except if it causes contagion, were included, patients duly authorized by the person responsible for the institution and who were able to undergo evaluation. Thirty-eight patients from the institution were evaluated, of which ten were excluded from the research according to pre-established criteria. More than 50% of participants were male, with an overall average age of 63.43 years. The characteristics related to nutritional status by NRS 2002 and MNA showed that the risk of malnutrition and its absence are associated with a wide age range. The MNA presents a more nuanced nutritional risk classification, showing that even 61% of the 96% of participants who would be out of nutrition risk, according to the NRS 2002, are “at risk of malnutrition”. Applying the MNA can demonstrate more conservative results than the NRS 2002.

关键词： Nursing Home Elderly Nutritional Risk Overweight

How small could a pup sound？ The physical bases of signaling body size in harbor seals

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Current Zoology 2017年第4期63卷 457-465页

作者： Andrea RAViGNANi Stephanie GROSS Maxime garcia ana RUBiO-garcia Bart DE BOER Veterinary & Research Department Sealcentre Pieterburen Hoofdstraat 94a Pieterburen AG 9968 The Netherlands Artificial intelligence Laboratory Vrije Universiteit Brussel Pleinlaan 2 Brussels 1050 Belgium Language and Cognition Department Max Planck Institute for Psycholinguistics Wundtlaan 1 Nijmegen XD 6525 The Netherlands institute for Terrestrial and Aquatic Wildlife Research University of Veterinary Medicine Hannover Foundation Werftstrasse 6 Buesum 25761 Germany ENES Lab/Neuro-PSi CNRS UMR9197 University of Lyon/Saint Etienne 23 rue Paul Michelon 42023 Saint-Etienne cedex 2 France

Vocal communication is a crucial aspect of animal behavior. The mechanism which most mam- mals use to vocalize relies on three anatomical components. First, air overpressure is generated in- side the lower vocal tract. Second, as the airstream goes through the glottis, sound is produced via vocal fold vibration. Third, this sound is further filtered by the geometry and length of the upper vocal tract. Evidence from mammalian anatomy and bioacoustics suggests that some of these three components may covary with an animal＇s body size. The framework provided by acoustic al- iometry suggests that, because vocal tract length （VTL） is more strongly constrained by the growth of the body than vocal fold length （VFL）, VTL generates more reliable acoustic cues to an animal＇s size. This hypothesis is often tested acoustically but rarely anatomically, especially in pinnipeds. Here, we test the anatomical bases of the acoustic allometry hypothesis in harbor seal pups Phoca vitulina. We dissected and measured vocal tract, vocal folds, and other anatomical features of 15 harbor seals post-mortem. We found that, while VTL correlates with body size, VFL does not. This suggests that, while body growth puts anatomical constraints on how vocalizations are filtered by harbor seals＇ vocal tract, no such constraints appear to exist on vocal folds, at least during puppy- hood. it is particularly interesting to find anatomical constraints on harbor seals＇ vocal tracts, the same anatomical region partially enabling pups to produce individually distinctive vocalizations.

关键词： acoustic allometry honest signaling larynx pinniped vocal tract.

A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-Martinez Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego De Leon-Oliva ana M.Gomez-Lahoz Jorge Monserrat Mar Atienza-Pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon Department of Medicine and Medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal institute of Sanitary Research(iRYCiS) 28034 MadridSpain Department of Psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain immune System Diseases‑Rheumatology Service and internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCi)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCi,explaining the progression and detrimental consequences related to this ***(PNiE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a *** initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and *** the present review,we will explore the most important local and systemic consequences of SCi from a PNiE perspective,defining the changes occurring in each system and how all these mechanisms are ***,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(SCi) Psychoneuroimmunoendocrinology(PNiE) Secondary injury immunoinflammatory dysfunction Gut microbiota Translational opportunities