bluuebunny/crossref_metadata_2025 huggingface dataset:
ROMA HUKUKUNDA SEÇİMLİK BORÇ (OBLIGATIO ALTERNATIVA) KAVRAMI ve SEÇİMLİK BORCUN İFASI
Authors: GÜNVEREN Güzide Burcu
Published: November 2021

Roma Hukukunda seçimlik borcun (obligatio alternativa) söz konusu durumlarda, borçlu iki veya daha fazla edimi borçlanır ancak bunlardan birinin ifasıyla da borcundan kurtulurdu (duae res in obligatione, una in solutione). “Köle Stichus ya da on As” vermeyi taahhüt etmek, seçimlik borcu örneklemektedir. Anlaşılacağı üzere çok edim ihtiva eden seçimlik borçta hangi edimin ifa edileceği hususunda belirsizlik vardır. Seçim hakkının kullanılması ile bu belirsizlik ortadan kalkardı. Seçim hakkını kullanmaya yetkili olan kişi seçimini yaptığı takdirde, edimlerden birisi kesin olarak borcun konusu haline gelirdi. Seçilen edim, borçlusu tarafından yerine getirildiği takdirde de borç sona ererdi. Seçim hakkı kural olarak borçluya aitti. Bununla beraber seçim hakkının tarafların anlaşmasına bağlı olarak alacaklıya ya da üçüncü kişiye de tanınması mümkündü. Roma Hukuku kaynaklarında, bilgiler çelişkili olsa da genel olarak borçlunun seçim hakkını, ifa anına kadar kullanabileceği kabul edilmektedir. Seçim hakkı alacaklıya tanınmış ise alacaklı, edimlerden birini talep ederse veya klasik devirde borçluya karşı dava açar ve litis contestatio ile istenilen edim bir kere tespit edilirse, seçiminden dönemezdi. Iustinianus Hukukunda ise alacaklı dava açarak edimlerden birini talep ettiği andan itibaren seçiminden dönemezdi.

Seçimlik borca konu olan edimlerden birinin borcun doğumundan sonra ifasının imkânsız hale gelmesi mümkündü. Seçim hakkının borçluya ait olduğu bir durumda borçlunun kusurundan kaynaklanan bir sebeple edimlerden biri imkânsız hale gelmişse, borç kalan edim üzerinde toplanırdı. Dolayısıyla bu ihtimalde borçlunun seçim hakkı sona ererdi. Çalışmamızda Roma Hukukunda seçimlik borç kavramı ele alınarak, seçimlik borcun diğer benzer kavramlar ile karşılaştırılması yapılmış, seçim hakkının özelliği açıklanmış ve hukuki metinlerin içerdiği bilgiler ışığında seçimlik borcun ifası açıklanmıştır.
A paksi atomerőmű hulladékainak cementbe ágyazása, és a technológiához tartozó vizsgáló laboratórium kialakítása
Authors: Baranyi Attila , Kopecskó Katalin , Feil Ferenc , Gric Lukáš
Published: November 2021

A Paksi Atomerőműben keletkező kis és közepes aktivitású hulladékok kezelésére a jelenleg létesítés alatt álló cementező technológiával új kompakt hulladékcsomagot hoznak létre, amely során a szilárd radioaktív hulladékot tartalmazó acélhordókat acélkonténerben helyezik el. A szilárd hulladékban és a hordók között lévő üregtérfogatot folyékony radioaktív hulladékok felhasználásával készült cementpéppel töltik ki. A kompakt hulladékcsomagoknak meg kell felelniük a Nemzeti Radioaktívhulladék-tároló Biztonsági jelentésében leírt hulladékátvételi követelményeinek. A még szintén létesítés alatt álló cementezett hulladékvizsgáló laboratórium feladata az elkészült cementpép tulajdonságainak gyártásközi ellenőrzése, valamint az ebből készült próbatestek nyomószilárdságának és kioldódási mértékének (diffúziós együttható) meghatározása. A laboratórium felszerelése és a cement/beton iparban használatos eszközök tesztelése során kiderült, hogy sok esetben speciális öntőformákra van szükség, a radioaktív cementpép kis viszkozitása és korrozív tulajdonságai miatt. Ezen kívül fontos követelmény, a radioaktív cementkő nyomószilárdságának mérése során keletkező törmelék összegyűjtése, és a kiporzás minimalizálása.
TO THE QUESTION OF THE PARTICIPATION OF A SPECIALIST DURING THE INVESTIGATION OF MALFEASANCES COMMITTED IN THE SPHERE OF BODIES OF LOCAL SELF GOVERNMENT
Authors: Сергеев Артём
Published: November 2021

The article is devoted to the acute issues of the participation of a specialist in certain investigative actions on the official malfeasance committed in the sphere of local self-government. Based on the specificity of the investigated criminal offences, in order to preliminary study of physical evidences and investigative actions, the author defines a range of specialists whose help is preferential during the investigation of such crimes.
LEGAL MEASURES OF THE STATE PREVENTION OF ETHNIC AND RELIGIOUS CONFLICTS
Authors: Аминов Ильдар
Published: November 2021

The article studies the ethnic and religious conflicts developed over the last years. The author comes to the conclusion that many disputable events of the geopolitical process and the administrative law forms of state activity are the main reasons for all these conflicts. This article finds the ways to solve eth- nic and religious conflicts, as well as it reviews modern means of preventing them. However a wide range of mechanisms to settle this problem isn’t able to resolve it. In this context the author tries to make a unique mechanism suitable for settlement or prevention of all conflicts, or at least the major part of them.
THE MEANING OF INTEREST IN OBLIGATIONS LEGAL RELATIONSHIP
Authors: Анисимов Владимир
Published: November 2021

The article is devoted to the topical questions of establishing the legal nature of interest and its role in civil law regulation of obligations, it also deals with the questions of the content of interest of each part of the obligation and the ways of their enforcement in the norms of civil law. It is concluded that the interest is the basis for the differentiation of civil law regulation of obligations.
ABOUT THE PRINCIPLES OF FINANCIAL LAW
Authors: Саттарова Нурия
Published: November 2021

According to the system of principles of law adopted in the theory of law, the basic principles of financial law and their classification are discussed. The author comes to the conclusion that at the present day the branch principles of financial law, emphasized in science, need to be clarified, as many of them are general legal principles with certain specific in this field of law.
ON THE TOPICAL LEGAL PROBLEMS OF THE ENVIRONMENT IN THE RUSSIAN FEDERATION (on the Case Material of the Republic of Bashkortostan)
Authors: Ибатуллина Наталья
Published: November 2021

The article deals with the environmental legislation of the Russian Federation. The author reveals environmental legislation problems, the topical problems are the following: authority distinction of the Federation and federal subjects, correspondence matters of the Federal laws and laws of the Russian Federation subjects, right of ownership to natural resources and more. Possible problems solutions are proposed.
Investigation of the Process of Dosing Compound Feed Components Using the DSh-100 Auger
Authors:   NGIEU, Bulatov S.Yu. , Nechaev V.N. ,   NGIEU, Sergeev A.G. ,   Doza-Agro LLC
Published: November 2021

The description of the design and the principle of operation of a system for dosing feed components for farm animals are provided. The results of studies of the operation of the DSh-100 auger as part of this system according to the criterion of dosing accuracy are presented. Regression models have been constructed and the optimal operating modes of the installation have been determined using these models.
NIETZSCHE FELSEFESİNDE ADALETİN KAYNAĞI VE İMKÂNI SORUNU
Authors: SABANCI Celal
Published: November 2021

Bu çalışma ile Nietzsche’nin adalet kavrayışı, onun eşitlik kavrayışı ve sözleşmeden türetilen bir birliktelikle ilgili düşünceleri çerçevesinde ele alınmıştır. Nietzsche adaletin kökenini mübadeleye, insanların bir sözleşmeyle bir araya gelme fikrini ise bir eşitlik varsayımına dayandırmaktadır. Ona göre bu eşitlik uydurulmuş bir eşitliktir. Doğanın kendisinde teşhis edemediğimiz bir adaletin ise insanlar arasında tesis edilebileceğine inanmak güçtür. İnsanlar kendi korunma ve güvenlik güdüleri dolayısıyla bencilce bir araya gelir. Kendi geçici çıkarları çerçevesinde konfor alanına çekilen insanlar, başlangıçtaki çıkar birliğini unutarak sözlerine riayet etmeyi bir erdem olarak kabullenirler. Nietzsche doğada olduğu gibi insanda da bir eşitsizlik olduğunu dile getirir. O, insanın doğası gereği gücü isteyeceğini belirterek, gücü arzulayan bir varlık olarak insanın bu gücü elde etmesi neticesinde başlangıçta kendi çıkarına olduğunu düşündüğü anlaşmayı ihlal edeceğini belirtir. Sosyal sözleşme kuramlarına dair eleştirilerinde Nietzsche bunları açıkça dile getirmektedir. Bu çalışma Nietzsche’nin adalet kavrayışını eşitlikle ve bu eşitliği tesis ettiği varsayılan sosyal sözleşme ile ilişkisinde değerlendirmek amacını taşımaktadır.
Comparative Clinical Analysis of Polymicrobial and Monomicrobial Bacterial Keratitis
Authors: Baek Seung Chul , Cho Chan-Ho , Lee Sang-Bumm
Published: November 2021

Purpose: We comparatively analyzed the microbiological profiles, predisposing factors, clinical aspects, and treatment outcomes of patients with polymicrobial and monomicrobial bacterial keratitis.Methods: A total of 194 cases of culture-proven bacterial keratitis treated between January 2007 and December 2016 were reviewed. Microbiological profiles, the epidemiology, predisposing factors, clinical characteristics, and treatment outcomes were compared between the polymicrobial group (polymicrobial bacterial keratitis [PBK]; 29 eyes, 62 isolates) and monomicrobial (monomicrobial bacterial keratitis [MBK]; 165 eyes, 165 isolates) group.Results: The most common isolates were Enterobacter (24%) in the PBK group and Staphylococcus (22%) in the MBK group. There were no significant differences between the two groups in previous ocular surface disease, previous ocular surgery, prior topical steroid use, epithelial defect size, and hypopyon. Age ≥60 years (PBK vs. MBK, 31% vs. 51%, p = 0.048), symptom duration (4.7 days vs. 8.0 days, p = 0.009), and contact lens use (34% vs. 18%, p = 0.036) were significantly different between the two groups. Regarding treatment outcomes, epithelial healing time ≥10 days, the final best-corrected visual acuity (BCVA), a need for surgical intervention, and the rate of poor clinical outcome were not significantly different between the two groups. Significant risk factors for a poor clinical outcome in all patients were an initial BCVA <0.1 (Z = 6.33, two-proportion Z-test), an epithelial defect size ≥5 mm2 (Z = 4.56), and previous ocular surface disease (Z = 4.36).Conclusions: Polymicrobial bacterial keratitis, compared to monomicrobial bacterial keratitis, was more significantly associated with younger age, contact lens use, and shorter symptom duration.
Short-term Comparison of Refractive Errors between Two Different Age Groups after LASEK for Moderate Myopia
Authors: Kim Mi Jeong , An Ji Seon , Moon Ja Yoon , Kim Hee Young , Choi Jin Seok , Pak Kyu Hong , Chung Sung Kun
Published: November 2021

Purpose: To investigate the safety of laser epithelial keratomileusis (LASEK) by drawing a comparison between two groups divided according to age (18-19 vs. 20-21 years old).Methods: The study was conducted as a retrospective analysis including 339 patients (678 eyes) who underwent LASEK between January 2017 and April 2020. Patients were divided by age group, group I (18-19 years old) and group II (20-21 years old). The objectives of the study included determination of visual acuity and refractive errors before and at 1, 3, and 6 months after the procedure.Results: The preoperative mean spherical equivalents (SEs) were -4.73 ± 0.88 diopters (D) in group I and -4.58 ± 0.87 D in group II (p = 0.34). At 1 month postoperatively, mean SEs were 0.32 ± 0.46 D in group I and 0.26 ± 0.59 D in group II (p = 0.18). At 3 months postoperatively, the mean SEs were 0.30 ± 0.47 D in group I and 0.28 ± 0.50 D in group II (p = 0.67). At 6 months postoperatively, the mean SEs were 0.15 ± 0.47 D in group I and 0.14 ± 0.50 D in group II (p = 0.89). There were no significant differences in postoperative best corrected visual acuity between group I and group II at 1, 3, or 6 months (p = 0.20, p = 0.13, and p = 0.11, respectively).Conclusions: There were no significant differences in postoperative mean SE or safety of LASEK between moderate myopia patients 18-19 years old and those 20-21 years old.
Subcutaneous Tocilizumab for Thyroid Eye Disease
Authors: Park Jungyul , Choi Hee-young
Published: November 2021

Purpose: To demonstrate the efficacy of subcutaneous tocilizumab (TCZ-SC) treatment for recalcitrant thyroid eye disease (TED) refractory to intravenous methylprednisolone (MP) and oral methotrexate (MTX).Case summary: (Case 1) A 52-year-old man, smoker, with hyperthyroidism presented with a 3-months history of TED. The initial clinical activity score (CAS) was 5 (total score of 7). High-dose intravenous MP and oral MTX failed to improve the symptoms. He was treated with four doses of 162 mg TCZ-SC at an interval of 2 weeks. Pre-treatment laboratory test results were within normal limits. CAS was reduced to 2 weeks after the final injection, and there were no recurrences during the 6-month follow-up. (Case 2) A 37-year-old woman, non-smoker, with a 3-months history of hyperthyroidism presented with conjunctival injection and upper eyelid erythema. The initial CAS was 4, and thyroid-stimulating immunoglobulin level was raised (475% of normal). The symptoms did not improve with 7.5 g intravenous MP and oral MTX. The patient was treated with 162 mg TCZ-SC. Pre-treatment laboratory test results were within normal limits. CAS was reduced to 1 after the final injection, and there were no recurrences during the 6-months follow-up.Conclusions: TCZ-SC improves symptoms of corticosteroid-resistant TED, and may be a reasonable option in recalcitrant TED cases. However, further studies are required to justify the use of TCZ-SC for TED.
Drug-Induced QT Interval Prolongation
Authors: Petric Domina
Published: November 2021

The correct measurement of the QT interval (using the QT correction formulas, preferably Fridericia and Framingham) as well as a correct interpretation of the causes and of the clinical consequences of a QT prolongation is very important in clinical practice. Drug-induced long QT syndrome (DILQTS) is one of the most common causes of LQTS. In the diagnosis and management of the DILQTS, it can be useful to follow the three-step rule presented in this article: detailed pharmacological anamnesis and correct ECG interpretation; database search and clinical interpretation; confirmatory test.
Beneficial effect of lithium in female patient with bipolar affective illness and psoriasis
Authors: Filipiak Przemysław , Jaskóła Anna , Gattner Karolina
Published: November 2021

Objectives. Psoriasis makes a relative contraindication for lithium treatment which can exacerbate its symptoms or induce it itself. On the other hand, lithium exerts immuno-modulatory activity.

Case study. In this paper, a case of a female patient is presented. The patient has been treated since 2012 for bipolar affective illness (bipolar disorder – BD) and psori­asis, which occurred for the first time during a depress­ive episode. Despite intensive pharmacological treatment, both as inpatient and outpatient, a satisfactory improvement of affective illness has not been obtained. After the introduction of lithium, a remission of BD was achieved as well as a reduction of psoriatic changes, which have been maintained until now (2021).

Conclusion. The remission of Bipolar Disorder (BD) on lithium can suggest that the patient belongs to the group of the so-called excellent lithium responders. In the presen­ted case remission of psoriasis was observed during lithium treatment. This case report must be treated with caution because remission could be spontaneous and the patient needs further observation.
ANALISIS PAHAM AL-ITTIHAD DAN AL-HULUL DALAM TRADISI TASAWUF ISLAM
Authors: Firmansyah Firmansyah
Published: November 2021

This research was conducted to find out how the concept of understanding al-ittihad and al-hulul in Islamic Sufism? and how is the influence of al-Ittihad and al-Hulul in the world of Sufism? This research is library research. Primary sources of research come from books on Sufism, mysticism or books relevant to the theme. As for enriching research information, secondary data sources are used from various books and journal articles that are relevant to this research. Research data collection was carried out using documentation techniques. The data analysis used inductive analysis. Based on the data analysis that has been carried out, it can be concluded that the notions of al-ittihad and al-hulul in their development gave a considerable influence on the development of philosophy, such as Al-Suhrawardi in Persia. In Turkey, this understanding contributed greatly to the creation of the Sufi mehfil which was developed by Jalaluddin Rumi. While in Indonesia, this understanding is very obvious in the understanding of manunggaling kawula gusti developed by Shaykh Siti Jenar. In relation to today's materialistic and hedonic human lifestyles, the concept of Sufism described in its understanding and teachings can be a medium to improve the increasingly complex social conditions of human life as a form of repressive action that can be taken.
Temporal trends of essential omega-3 fatty acids in Atlantic and Pacific food webs as measured in eggs of Leach’s storm-petrel Oceanodroma leucorhoa
Authors: Hebert CE , Burgess NM , Elliott JE
Published: November 2021

Leach’s storm-petrel Oceanodroma leucorhoa populations in the North Atlantic have declined in recent decades. The cause of those declines is not clear but one potential contributing factor could be reductions in the availability of essential nutrients due to changing marine ecology resulting from global warming. One group of particular concern is the omega-3 highly unsaturated fatty acids (n-3 HUFAs), in particular, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Dietary sources of EPA and DHA are required for normal growth and development in higher consumers, including birds. However, previous work has predicted increases in sea surface temperatures may cause declines in their availability. Here, we investigate this possibility by examining temporal trends (1992-2015) in EPA and DHA concentrations in Leach’s storm-petrel eggs from 5 Canadian colonies: 2 on the Atlantic coast (Gull, Kent Islands) and 3 on the Pacific coast (Hippa, Storm, Cleland Islands). Neither EPA nor DHA concentrations in eggs decreased with time on either coast; rather, on the Atlantic coast, both EPA and DHA increased over the period of study. Carbon stable isotopes in the same eggs indicated that storm-petrels foraging in offshore, pelagic waters may have had increased access to n-3 HUFA. The data generated here provide a baseline for future comparisons. Ongoing regular monitoring of fatty acids in seabird eggs would be prudent given the likelihood of further increases in ocean temperatures.
From Metapsychology to Magnetic Gnosis: An Esoteric Context for Interpreting Traumatic Modes of Transcendence in Sándor Ferenczi'sClinical Diaryand Elizabeth Severn'sThe Discovery of the Self
Authors: Boyle John
Published: November 2021

It has been argued that the essential themes in Sándor Ferenczi's Clinical Diary (1932) centre around three major axes (theoretical, technical and personal). This paper proposes a fourth: namely, an occult or esoteric axis. To make the case for its presence in the Clinical Diary, the article provides a brief introduction to the academic study of Western esotericism in order to more adequately situate its proximate fin de siècle occult precursors vis-à-vis psychoanalytic metapsychology. A brief account of Ferenczi's correspondence with Freud on the role of the occult in psychoanalysis is then provided. This constitutes the necessary context for embarking upon an investigation into the ‘psychognostic’ metapsychology co-developed during the course of Ferenczi's ‘mutual analysis’ with the so-called ‘evil genius’, Elizabeth Severn. By way of conclusion, James Grotstein's account of a ‘numinous and immanent psychoanalytic subject’ is highlighted as the locus for a synergistic rapprochement between pre-Freudian and contemporary psychoanalytic conceptualizations of the subject congruent with the ‘Orphic trajectory’ outlined in this paper.
The Global Crisis of 2008 and Investigation of the Reaction of Other Macroeconomic Factors to A Shock on the Unemployment Factor of the Countries: An Application Developed and Developing Countries
Authors: ARSLAN Merve , ARSLAN Hamide , GENÇER ÇELİK Gülşah
Published: November 2021

All countries of the world were affected by the global mortgage crisis that took place in 2008. It is referred to as the new generation financial crisis type. Underdeveloped countries were more affected by the crises experienced in the past, whereas the 2008 crisis affected the developed economies more deeply. 31 countries were selected in this study. In the study, 18 developed countries and 13 developing countries were included. The changes in unemployment rates of countries in the post-crisis period are discussed. Then, it is aimed to investigate the reactions of other macroeconomic factors to a shock in the unemployment factor of countries with VAR analysis.
A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss
Authors: Yao Cong , Zhu Meisong , Han Xiuguo , Xu Qiang , Dai Min , Nie Tao , Liu Xuqiang
Published: November 2021

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.
A Fluorescent Aptasensor Based on Assembled G-Quadruplex and Thioflavin T for the Detection of Biomarker VEGF165
Authors: Zheng Xin , Gao Shunxiang , Wu Jihong , Hu Xiaobo
Published: November 2021

VEGF165, a regulator of angiogenesis, has been widely used as a serum biomarker for a number of human diseases, including cancer, rheumatoid arthritis, bronchial asthma, and diabetic eye disease. The rapid, accurate, and convenient detection of VEGF165 is a crucial step in effective healthcare monitoring, disease diagnosis, and prognosis assessment. In this study, a fluorescent aptasensor based on an assembled G-quadruplex and the signal molecule ThT was developed for VEGF165 detection. First, G-rich DNA fragments were assembled at both ends of the anti-VEGF165 aptamer, and the B-DNA form was converted into a G-quadruplex structure aptamer (G4-Apt). Then, ThT was introduced, and the G-quadruplex significantly enhanced the fluorescence intensity of the bound ThT. When VEGF165 was present, the higher affinity of the aptamer to the target protein allowed the G4-Apt/VEGF165 complex to form and release ThT, which emitted only weak fluorescence in the free state. Therefore, the aptasensor exhibited a good linear detection window from 1.56 to 25 nM VEGF165, with a limit of detection of 0.138 nM. In addition, the aptasensor was applied to detect VEGF165 in clinical serum samples, showing good accuracy, reproducibility, and stability. These results indicate that our developed fluorescent aptasensor can potentially be a reliable, convenient, and cost-effective approach for the sensitive, specific, and rapid detection of the VEGF165 biomarker.
Bioprocess of Microbial Melanin Production and Isolation
Authors: Choi Kwon-Young
Published: November 2021

Melanin is one of the most abundant pigments found in the biosphere. Owing to its high biocompatibility and diverse biological activities, it has been widely applied as a functional biomaterial in the cosmetic, pharmaceutical, biopolymer, and environmental fields. In this study, the production of melanin was comprehensively reviewed concerning bioconversion and isolation processes. First, several melanogenic microbes, including fungi and bacteria, were summarized. Melanin production was classified by host and melanin type and was analyzed by titers in g/L in addition to reaction conditions, including pH and temperature. The production was further interpreted using a space-time yields chart, which showed two distinct classifications in productivity, and reaction conditions were analyzed using a pH-temperature-titer chart. Next, the extraction process was summarized by crude and pure melanin preparation procedures, and the extraction yields were highlighted. Finally, the recent applications of melanin were briefly summarized, and prospects for further application and development in industrial applications were suggested.
Spider Toxin Peptide-Induced NIR Gold Nanocluster Fabrication for GSH-Responsive Cancer Cell Imaging and Nuclei Translocation
Authors: Tan Huaxin , Liu Sisi , He Yaolin , Cheng Guofeng , Zhang Yu , Wei Xiaojie , Hu Lidan
Published: November 2021

Goldnanoclusters (GNCs) have become a promising nanomaterial for bioimaging because of their unique optical properties and biocompatibility. In this study, lycosin-I peptide, which possesses a highly selective anticancer activity by affecting the permeability of cancer cell membrane, was firstly modified for constructing fluorescent GNCs (LGNCs) for bioimaging of tumor cells. The obtained LGNCs exhibited strong near-infrared (NIR) fluorescence, which can be further enhanced by the peptide-induced aggregation and selectively stained three cancerous cell lines over normal cell lines with low intrinsic toxicity. After uptake by tumor cells, LGNC aggregates can be depolymerized into ultrasmall nanoclusters by high-level glutathione (GSH) and realize the nuclear targeting translocation. Collectively, our work suggests the potential of natural active biomolecules in designing NIR fluorescent GNCs for bioimaging.
The Role of Biodegradable Magnesium and Its Alloys in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-Analysis Based on Animal Studies
Authors: Shang Zhizhong , Li Dongliang , Chen Jinlei , Wang Mingchuan , Zhang Baolin , Wang Xin , Ma Bin
Published: November 2021

Objective: The actual efficacy of magnesium and its alloy in anterior cruciate ligament reconstruction (ACLR) was systematically evaluated to reduce the risk of translation from animal experiments to the clinic.

Methods: Databases of PubMed, Ovid-Embase, Web of Science, CNKI, Wanfang, VIP, and CBM were searched for literature in July 2021. Screening of search results, data extraction, and literature quality evaluation were undertaken independently by two reviewers.

Results and discussion: Seven articles were selected for the meta-analysis. The results showed that the mechanical properties of the femoral-tendon graft–tibia complex fixed with magnesium and its alloys were comparable to those fixed with titanium and its alloys, and magnesium and its alloys were superior to titanium and its alloys in promoting new bone formation. In addition, the unique biodegradability made magnesium and its alloys an orthopedic implant with significant therapeutic potential. However, whether the degradation rate of magnesium and its alloy can match the rate of bone-tendon integration, and whether the bioconjugation of bone-tendon after degradation can meet the exercise load still needs to be explored in further detail. Simultaneously, it is necessary for future research to improve and standardize experimental design, result measurement, etc., so as to minimize the risk of transforming animal experimental results into clinical practice.
The Emerging Role of m6A Modification in Regulating the Immune System and Autoimmune Diseases
Authors: Wang Yimeng , Li Lifang , Li Jiaqi , Zhao Bin , Huang Gan , Li Xia , Xie Zhiguo , Zhou Zhiguang
Published: November 2021

Over the past several decades, RNA modifications have rapidly emerged as an indispensable topic in epitranscriptomics. N6-methyladenosine (m6A), namely, methylation at the sixth position of an adenine base in an RNA molecule, is the most prevalent RNA modification in both coding and noncoding RNAs. m6A has emerged as a crucial posttranscriptional regulator involved in both physiological and pathological processes. Based on accumulating evidence, m6A participates in the pathogenesis of immune-related diseases by regulating both innate and adaptive immune cells through various mechanisms. Autoimmune diseases are caused by a self-destructive immune response in the setting of genetic and environmental factors, and recent studies have discovered that m6A may play an essential role in the development of autoimmune diseases. In this review, we focus on the important role of m6A modification in biological functions and highlight its contributions to immune cells and the development of autoimmune diseases, thereby providing promising epitranscriptomic targets for preventing and treating autoimmune disorders.
Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing
Authors: Fan Chang , Ma Yanzhen , Chen Sen , Zhou Qiumei , Jiang Hui , Zhang Jiafu , Wu Furong
Published: November 2021

N6-Methyladenosine (m6A), a unique and common mRNA modification method in eukaryotes, is involved in the occurrence and development of many diseases. Liver fibrosis (LF) is a common response to chronic liver injury and may lead to cirrhosis and even liver cancer. However, the involvement of m6A methylation in the development of LF is still unknown. In this study, we performed a systematic evaluation of hepatic genome-wide m6A modification and mRNA expression by m6A-seq and RNA-seq using LF mice. There were 3,315 genes with significant differential m6A levels, of which 2,498 were hypermethylated and 817 hypomethylated. GO and KEGG analyses illustrated that differentially expressed m6A genes were closely correlated with processes such as the endoplasmic reticulum stress response, PPAR signaling pathway and TGF-β signaling pathway. Moreover, a total of 90 genes had both a significant change in the m6A level and mRNA expression shown by joint analysis of m6A-seq and RNA-seq. Hence, the critical elements of m6A modification, including methyltransferase WTAP, demethylases ALKBH5 and binding proteins YTHDF1 were confirmed by RT-qPCR and Western blot. In an additional cell experiment, we also observed that the decreased expression of WTAP induced the development of LF as a result of promoting hepatic stellate cell (HSC) activation. Therefore, this study revealed unique differential m6A methylation patterns in LF mice and suggested that m6A methylation was associated with the occurrence and course of LF to some extent.
Mechanisms Underlying Hox-Mediated Transcriptional Outcomes
Authors: Cain Brittany , Gebelein Brian
Published: November 2021

Metazoans differentially express multiple Hox transcription factors to specify diverse cell fates along the developing anterior-posterior axis. Two challenges arise when trying to understand how the Hox transcription factors regulate the required target genes for morphogenesis: First, how does each Hox factor differ from one another to accurately activate and repress target genes required for the formation of distinct segment and regional identities? Second, how can a Hox factor that is broadly expressed in many tissues within a segment impact the development of specific organs by regulating target genes in a cell type-specific manner? In this review, we highlight how recent genomic, interactome, and cis-regulatory studies are providing new insights into answering these two questions. Collectively, these studies suggest that Hox factors may differentially modify the chromatin of gene targets as well as utilize numerous interactions with additional co-activators, co-repressors, and sequence-specific transcription factors to achieve accurate segment and cell type-specific transcriptional outcomes.
Elevated Fasting Plasma Glucose Is Associated With an Increased Risk of MCI: A Community-Based Cross-Sectional Study
Authors: Li Wei , Yue Ling , Sun Lin , Xiao Shifu
Published: November 2021

Background

Mild cognitive impairment (MCI) is a transitional state between normal elderly people and dementia, with a higher risk of dementia transition. The primary purpose of the current study was to investigate whether routine blood and blood biochemical markers could be used to predict the onset of MCI.

Methods

Data was obtained from the cohort study on brain health of the elderly in Shanghai. A total of 1015 community elders were included in the current study. Based on clinical evaluation and the scores of Montreal Cognitive Assessment (MoCA), these participants were divided into the MCI (n=444) and cognitively normal groups (n=571). Then we tested their fasting blood routine and blood biochemical indexes, and collected their general demographic data by using a standard questionnaire.

Results

By using binary logistic regression analysis and the ROC curve, we found that elevated fasting plasma glucose (p=0.025, OR=1.118, OR=1.014-1.233) was a risk factor for MCI.

Conclusions

Elevated fasting blood glucose may be a risk factor for mild cognitive impairment, but the above conclusions need to be verified by longitudinal studies.
Obesity Exacerbates Irritable Bowel Syndrome-Related Sleep and Psychiatric Disorders in Women With Polycystic Ovary Syndrome
Authors: Tseng Ping-Huei , Chiu Han-Mo , Tu Chia-Hung , Wu Ming-Shiang , Ho Hong-Nerng , Chen Mei-Jou
Published: November 2021

Background/Objectives

Polycystic ovary syndrome (PCOS) and irritable bowel syndrome (IBS) share similar clinical and psychosocial features. We aimed to investigate the clinical characteristics of IBS in women with PCOS, and its relationship with obesity, metabolic and hormonal profiles, as well as sleep and psychiatric disorders.

Subjects/Methods

This is a cross-sectional case-control study of 431 untreated women with PCOS and 259 healthy volunteers. All participants were assessed with a comprehensive clinical evaluation and two questionnaires: the Athens Insomnia Scale (AIS) and the Brief Symptom Rating Scale (BSRS-5). IBS was diagnosed using the Rome III criteria. Obesity was defined as a BMI ≥30 kg/m2. Anthropometric measurements, metabolic, hormonal profiles, and psychosocial morbidities were compared.

Results

Women with PCOS were more likely to have IBS (10.7% vs 5.8%, p=0.029) and obesity (29% vs 4%, p<0.001) than healthy volunteers. Mixed-type IBS (IBS-M) was the most common subtype (74%) among patients with PCOS and IBS. There was a higher prevalence of psychiatric morbidities (total BSRS-5 score ≥10) in women with PCOS than in healthy women (11.4% vs 3.5%, p<0.001). Women with PCOS and IBS were more likely to have sleep difficulties (67.4% vs 30.9%, p<0.001) and psychiatric morbidities (21.7% vs 10.1%, p=0.019) than those without IBS. Anthropometrics, metabolic and hormonal profiles were similar between PCOS women with and without IBS. Among women with PCOS, those with both IBS and obesity had the highest risk of developing sleep difficulties (odds ratio: 5.91; 95% confidence interval: 1.77–19.77) and psychiatric distress (odds ratio: 4.39; 95% confidence interval: 1.26–15.29) than those without.

Conclusion

Women with PCOS have increased IBS, obesity, sleep and psychiatric disturbances. The presence of IBS in PCOS women is associated with sleep and psychiatric disorders. The coexistence of obesity and IBS exacerbates sleep difficulties and psychiatric distress. Screening and management of IBS and obesity might be warranted to improve sleep and psychiatric disturbances in women with PCOS.
Space and Species Interactions in Welfare Estimates for Invasive Species Policy
Authors: Brockmann Stephanie , Zhang Hongyan , Mason Doran M. , Rutherford Edward S.
Published: November 2021

Aquatic invasive species (AIS) can cause catastrophic damages to lake ecosystems. Bigheaded carp are one such species that pose a current threat to Lake Michigan. Bigheaded carp are expected to have spatially differentiated impacts on other aquatic species in the metapopulation. Policymakers must decide how much to invest in mitigation or conservation policies, if at all, by understanding how invasions impact social welfare or social wellbeing. Estimates of social welfare implications, however, may be biased if important interactions between species and space are overly simplified or aggregated out of the model. In this analysis, a bioeconomic model that links an ecological model with an economic model of recreational fishing behavior is used to complete a comparative analysis of the social welfare implications across several different ecological specifications to demonstrate what biases exist if species interactions are neglected or if ecological characteristics are assumed to be homogenous across space. Results of the bigheaded carp case study suggest that social welfare losses from the invasion vary substantially if species interactions are excluded and vary less if space is treated homogeneously.
Establishment of an Efficient Protoplast Regeneration and Transfection Protocol for Field Cress (Lepidium campestre)
Authors: Sandgrind Sjur , Li Xueyuan , Ivarson Emelie , Ahlman Annelie , Zhu Li-Hua
Published: November 2021

Field cress (Lepidium campestre) is a potential oilseed crop that has been under domestication in recent decades. CRISPR/Cas9 is a powerful tool for rapid trait improvement and gene characterization and for generating transgene-free mutants using protoplast transfection system. However, protoplast regeneration remains challenging for many plant species. Here we report an efficient protoplast regeneration and transfection protocol for field cress. Important factors such as type of basal media, type/combination of plant growth regulators, and culture duration on different media were optimized. Among the basal media tested, Nitsch was the best for protoplast growth in MI and MII media. For cell wall formation during the early stage of protoplast growth, relatively high auxin concentrations (0.5 mg L−1 NAA and 2,4-D), without addition of cytokinin was preferred for maintaining protoplast viability. After cell wall formation, 1.1 mg L−1 TDZ combined with either 0.05 mg L−1 NAA or 2,4-D was found to efficiently promote protoplast growth. On solid shoot induction medium, 1.1 mg L−1 TDZ without any auxin resulted in over 80% shoot generation frequency. A longer culture duration in MI medium would inhibit protoplast growth, while a longer culture duration in MII medium significantly delayed shoot formation. Using this optimized protoplast regeneration protocol, we have established an efficient PEG-mediated transfection protocol using a vector harboring the GFP gene, with transfection efficiencies of 50–80%. This efficient protoplast protocol would facilitate further genetic improvement of field cress via genome editing, and be beneficial to development of protoplast regeneration protocols for related plant species.
Integrated Lipidomic and Transcriptomic Analysis Reveals Lipid Metabolism in Foxtail Millet (Setaria italica)
Authors: Zhang Haiying , Wang Junyou , Zhao Jing , Sun Changqing , Wang Jin , Wang Qian , Qu Fei , Yun Xiaodong , Feng Zhiwei
Published: November 2021

Foxtail millet (Setaria italica) as the main traditional crop in China, is rich in many kinds of high quality fatty acids (FAs). In this study, Ultra-high performance liquid chromatography-time-of-flight-tandem mass spectrometer (UHPLC-Q-TOF-MS/MS) was used to determine the lipids of JG35 and JG39. A total of 2,633 lipid molecules and 31 lipid subclasses were identified, mainly including thirteen kinds of glycerophospholipids (GP), eleven kinds of glycerolipids (GL), four kinds of sphingolipids (SP), two kinds of fatty acyls (FA) and one kind of sterol (ST). Among them JG35 had higher contents of diacylglycerols (DG) and ceramides (Cer), while triacylglycerols, phosphatidyl ethanolamine, phosphatidic acid, sterol, fatty acyls and pardiolipin (TG, PE, PA, ST, FA and CL) were higher in JG39. Meantime, the correlation analysis of lipidomics and transcriptomics was used to map the main differential lipid metabolism pathways of foxtail millet. The results shown that a differentially expressed genes (DEGs) of FATA/B for the synthesis of FA was highly expressed in JG35, and the related genes for the synthesis DG (ACCase, KAS, HAD, KCS, LACS and GAPT), TG (DGAT and PDAT) and CL (CLS) were highly expressed in JG39. The results of this study will provide a theoretical basis for the future study of lipidomics, improvement of lipid quality directionally and breeding of idiosyncratic quality varieties in foxtail millet.
Age-Based Disparities in Metastatic Melanoma Patients Treated in the Immune Checkpoint Inhibitors (ICI) Versus Non-ICI Era: A Population-Based Study
Authors: Safi Mohammed , Al-Azab Mahmoud , Jin Chenxing , Trapani Dario , Baldi Salem , Adlat Salah , Wang Aman , Ahmad Bashir , Al-madani Hamza , Shan Xiu , Liu Jiwei
Published: November 2021

Immune checkpoint inhibitors (ICIs) have revolutionized metastatic melanoma treatment, but our knowledge of ICI activity across age groups is insufficient. Patients in different age groups with advanced melanoma were selected based on the ICI approval time in this study. Patients with melanoma were identified in the Surveillance, Epidemiology, and End Result (SEER) database program 2004–2016. The results showed that 4,040 patients had advanced melanoma before the advent of ICI (referred to as the “non-ICI era”), whereas there were 6,188 cases after ICI approval (referred to as the “ICI era”). In all age groups, the cases were dominated by men. The differences between the first (20–59 years) and second (60–74 years) age groups in both eras were significant in terms of surgery performance and holding of insurance policies (p = 0.05). The first and second groups (20–59 and 60–70 years old, respectively) showed no difference in survival (median = 8 months) during the non-ICI era, but the difference was evident in the first, second, and third age groups in the ICI era, with the younger group (20–59 years) having significantly better survival (median = 18, 14, and 10 months, respectively, p = 0.0001). Multivariate analysis of the first group (the youngest) in the ICI era revealed that surgery was significantly associated with an increase in survival among patients compared with those who did not undergo surgery (p < 0.0001). Furthermore, having an insurance policy among all age groups in the ICI era was associated with favorable survival in the first (20–59 years) and second (60–74 years) age groups (p = 0.0001), while there were no survival differences in the older ICI group (>74 years). Although there were differences in survival between the ICI era and the non-ICI era, these results demonstrate that ICI positively affected the survival of younger patients with advanced melanoma (first age group) than it had beneficial effects on older patients. Moreover, having had cancer surgery and holding an insurance policy were positive predictors for patient survival. This study emphasizes that adequate clinical and preclinical studies are important to enhance ICI outcomes across age groups.
Systems Biology to Understand and Regulate Human Retroviral Proinflammatory Response
Authors: Helmy Mohamed , Selvarajoo Kumar
Published: November 2021

The majority of human genome are non-coding genes. Recent research have revealed that about half of these genome sequences make up of transposable elements (TEs). A branch of these belong to the endogenous retroviruses (ERVs), which are germline viral infection that occurred over millions of years ago. They are generally harmless as evolutionary mutations have made them unable to produce viral agents and are mostly epigenetically silenced. Nevertheless, ERVs are able to express by still unknown mechanisms and recent evidences have shown links between ERVs and major proinflammatory diseases and cancers. The major challenge is to elucidate a detailed mechanistic understanding between them, so that novel therapeutic approaches can be explored. Here, we provide a brief overview of TEs, human ERVs and their links to microbiome, innate immune response, proinflammatory diseases and cancer. Finally, we recommend the employment of systems biology approaches for future HERV research.
Combined Deficiency of the Melanocortin 5 Receptor and Adenosine 2A Receptor Unexpectedly Provides Resistance to Autoimmune Disease in a CD8+ T Cell-Dependent Manner
Authors: McDonald Trisha , Muhammad Fauziyya , Peters Kayleigh , Lee Darren J.
Published: November 2021

Regulatory immunity that provides resistance to relapse emerges during resolution of experimental autoimmune uveitis (EAU). This post-EAU regulatory immunity requires a melanocortin 5 receptor (MC5r)-dependent suppressor antigen presenting cell (APC), as shown using a MC5r single knock-out mouse. The MC5r-dependent APC activates an adenosine 2A receptor (A2Ar)-dependent regulatory Treg cell, as shown using an A2Ar single knock-out mouse. Unexpectedly, when MC5r-/-post-EAU APC were used to activate A2Ar-/-post-EAU T cells the combination of cells significantly suppressed EAU, when transferred to EAU mice. In contrast, transfer of the reciprocal activation scheme did not suppress EAU. In order to explain this finding, MC5r-/-A2Ar-/-double knock-out (DKO) mice were bred. Naïve DKO mice had no differences in the APC populations, or inflammatory T cell subsets, but did have significantly more Treg cells. When we examined the number of CD4 and CD8 T cell subsets, we found significantly fewer CD8 T cells in the DKO mice compared to WT and both single knock-out mice. DKO mice also had significantly reduced EAU severity and accelerated resolution. In order to determine if the CD8 T cell deficiency contributed to the resistance to EAU in the DKO mice, we transferred naïve CD8 T cells from WT mice, that were immunized for EAU. Susceptibility to EAU was restored in DKO mice that received a CD8 T cell transfer. While the mechanism that contributed to the CD8 T cell deficiency in the DKO mice remains to be determined, these observations indicate an importance of CD8 T cells in the initiation of EAU. The involvement of CD4 and CD8 T cells suggests that both class I and class II antigen presentation can trigger an autoimmune response, suggesting a much wider range of antigens may trigger autoimmune disease.