bluuebunny/crossref_metadata_2025 huggingface dataset:
KINERJA PANITIA PEMILIHAN KECAMATAN (PPK) DALAM PEMILIHAN UMUM (UMUM) SERENTAK TAHUN 2019 DI KECAMATAN SAGULUNG
Authors: Ahmad Ardyanti , Solihin Muhammad , Lestari Linayati
Published: September 2022

PPK dalam Pemilihan Umum dianggap unsur yang khusus karena termasuk sebagai ujung tombak penyelenggara dalam menyelesaikan masalah terkhusus data pemilih. Tujuan dari penelitian ini adalah untuk mengetahui kinerja PPK terhadap penyelenggaraan pemilihan umum serentak tahun 2019 di Kecamatan Sagulung khususnya pada data pemilih yang bermasalah. Berdasarkan hasil penelitian, diketahui bahwa Kinerja PPK di Kecamatan Sagulung masih belum maksimal dikarenakan oleh adanya beberapa indikator yang belum termaksimalkan dalam segi pertama Kualitas yang kurang menyeluruh dalam hal sosialisasi PPK Sagulung terhadap Pantarlih yang melakukan pendataan Coklit di lapangan, KPPS yang melakukan rekapitulasi pleno dan masyarakat yang masih kurang paham akan adanya Pemilu Serentak 2019 yang berbasis E-KTP.  Kedua Kuantitas Kinerja PPK Sagulung belum cukup baik karena penyelenggara pemilu di Kecamatan Sagulung terkhusus PPK terkait sosialisasi bimbingan teknik (BIMTEK) terhadap KPPS yang masih belum optimal. Pada tahapan Data yang berlangsung lama juga membuat petugas lapangan menjadi kewalahan untuk memverifikasi di lapangan. Pada tahap rekapitulasi, memakan waktu yang lama dikarenakan gedung kurang memadai untuk dilakukan pleno dengan banyak panel akibatnya jadwal selesai pleno mundur tidak sesuai jadwal. Kemudian ketiga  dalam hal Efisiensi Pelaksanaan tugas PPK Sagulung telah melaksanakan semua tahapan-tahapan Pemilu sesuai dengan peraturan dan perundang-undangan yang ada.
The use of magnesium in arythmology
Authors: Balashova N. V. , Orlova S. V. , Gulia L. D. , Benia R. M. , Nikitina E. A.
Published: September 2022

Optimal nutrition is one of the main factors for a normal heart rhythm, which includes all essential macro- (proteins, fats, carbohydrates) and micronutrients (vitamins and minerals). Numerous studies have found that magnesium is one of the key minerals for the cardiovascular system. Its deficiency in the diet increases the risk of developing cardiovascular accidents. Hypomagnesemia is associated with unstable electrical repolarization of the heart and contributes to sudden death in heart failure. Replenishment of magnesium deficiency in nutrition, diagnosis of hypomagnesemia, selection of magnesium preparations considering bioavailability are of great importance in the tactics of clinicians. The use of magnesium in complex therapy helps to reduce the risk of developing arrhythmias, including postoperative atrial fibrillation, ventricular arrhythmias and arrhythmias in myocardial infarction.
An Ode to Curcumin: One Hundred Mechanisms of Curcumin’s Effectiveness Against Human Pathological Conditions
Authors: Orlova S. V. , Nikitina E. A. , Prokopenko E. V. , Balashova N. V. , Vodolazkaya A. N.
Published: September 2022

Currently, a large amount of experimental data has been accumulated, which confirm that the main component of turmeric, curcumin, has a high biological activity and a wide spectrum of action. Curcumin is used in the practice of clinical medicine as an effective anti-inflammatory, antioxidant, neuroprotective, detoxifying and antiseptic agent. Based on numerous reviews of clinical studies, it seems possible to use this biologically active substance in therapy as a universal remedy for the prevention of the development and complex treatment of many pathological conditions.
On the issue of raising students’ awareness of healthy nutrition using modern information technologies (analytical review)
Authors: Gorelova Zh. Yu. , Zaretskaya A. R. , Solovieva Yu. V. , Letuchaya T. A.
Published: September 2022

The ways of using modern digital resources as a tool for motivating and controlling proper nutrition in the choice of food products by schoolchildren are presented. The review provides literature sources for monitoring schoolchildren’s dietary preferences. Analyzed information platforms to raise students’ awareness of healthy eating. Digital technologies provide up-to-date information on healthy eating, healthy lifestyles and can help children and adolescents develop healthy eating habits and cultures. When using digital technologies, it is necessary to carry out educational work with children, with parents, and teachers. The results of the effectiveness of educational programs depend on a properly organized set of preventive measures using modern means of education and communication.
Analysis of survival and timing of non-lethal complications after mitral valve replacement with mechanical prostheses
Authors: Markova M. M. , Polunina O. S. , Tarasov D. G. , Tsverkunova O. V. , Polunina E. A.
Published: September 2022

The aim of the study. To study the structure of lethal and non-lethal complications with an analysis of survival and the likelihood of non-lethal complications after mitral valve (MV) replacement with bicuspid mechanical prostheses over a five-year period.   Materials and methods. The data of 260 patients who were treated in the period of 2012–2014 were analyzed a surgical intervention was performed – isolated MV prosthetics with mechanical bivalve prostheses. Among the patients, there were 84 (32.3 %) men and 176 (67.7 %) women. The median age was 51.0 [44.0–55.5] years. Statistical analysis was carried out using IBM SPSS Statistics 26.0 (USA).   Results of the study and conclusions. According to the results of the five-year survival after MV prosthetics with mechanical prostheses, it was 86.6 %. At the same time, acute cardiovascular diseases (myocardial infarction, cardiac arrhythmias) were the leading cause of death. Among non-lethal thromboembolic complications, acute cerebrovascular accident prevailed, it developed in 65.3 %. Among nonlethal hypocoagulation complications, nosebleeds were most often recorded – in 40.5 % of patients. The probability of developing non-lethal thromboembolic complications by the fifth year is 20.0 % vs 18.5 % in the first six months after prosthetics with mechanical prostheses. And the probability of developing non-lethal hypocoagulation complications by the fifth year is 26.8 % vs 6.1 % in the first six months after prosthetics with mechanical prostheses.
Protocol of bedside ultrasound examination for heart failure (ConCOrD – CONgestion, Cardiac and multiORgan Dysfunction)
Authors: Kochmareva E. A. , Mikhei R. Yu. , Lykhin V. N. , Filyavin R. E. , Solov’ev V. S.
Published: September 2022

The purpose of this article is to discuss an algorithm for bedside ultrasound examination in patients with heart failure, which consisting of three blocks: assessment of morphofunctional cardiac pathology, detection of hypertension in the heart chambers, and the presence of congestion. This protocol is based on the point-of-care ultrasound methodology and is designed for use by doctors of clinical non-ultrasound specialties. The protocol is presented in two variations: extended (for expert cardiological assessment) and short for emergency examination. The article provides brief information about the diagnosis, terminology, and classification of heart failure according to modern clinical guidelines.
Features of providing medical care to patients with extensive high-voltage electric burns
Authors: Alekseev A. A. , Bobrovnikov A. E. , Chilikin N. M. , Bogdanov V. V.
Published: September 2022

Electrical injuries are a serious problem around the world. Patients with extensive, high-voltage electric burns belong to the group of severely burned. Timely and adequate treatment, which includes intensive anti-shock measures in the first days after injury, with simultaneous active surgical tactics, is decisive for saving life for such victims. The provision of specialized, high-tech medical care for these complex patients is optimal in conditions of a burn department / center of a multidisciplinary medical organization. However, knowledge of the basic principles of providing emergency and urgent medical care to victims with electrical trauma even before admission to the burn hospital is the key to their further successful treatment.
RESULTS of MORPHOLOGICAL ANALYSIS of ANIMAL HARD TISSUES IN NORMAL AND SIMULATED OSTEOPOROSIS USING A NON-INVASIVE COMPUTED MICROTOMOGRAPHY TECHNIQUE
Authors: Dolgalev A. , Rzhepakovsky I. , Danaev A. , Avanisyan V. , Shulga G. , Korobkeev A.
Published: September 2022

Introduction. X-ray microtomography is a non-destructive method of microstructural analysis, which has a high level of detail and allows the possibility of assessing the internal architecture of organs and tissues using 3D-analysis[1]. The speciﬁcs of working with such equipment can be divided into in vivo and in vitro, i.e. working with live laboratory animals (mice, rats, rabbits) under anesthesia or studying organs and tissues separated from the animal [2].

The aim of the work was to study the microstructure of sheep bone tissues in normal and simulated osteoporosis using computed microtomography.

Materials and methods. We performed microCT analysis of different sheep bones in normal and experimental osteoporosis. Bone tissue of the jaw, iliac and femur, and teeth were collected from control and experimental animals. Bone tissue samples were ﬁxed in 10% buffered formalin. X-ray microCT scanner Skyscan 1176 (BrukermicroCT, Belgium) and software Skyscan 1176 control program (10.0.0.0), Nrecon (1.7.4.2), DataViewer (1.5.6.2), CT-analyser (1.18.4.0), CTvox (3.3.0r1403) were used to scan and process materials.

Results. MicroCT examination and 3D-imaging conﬁrmed the elimination of trabeculae in the metaphyseal region of the femur in sheep with experimental osteoporosis from the centre to the periphery; in addition, 3D-analysis showed a 15.1% decrease in bone percentage, a 7.8% decrease in bone mineral density, and an increase in Tb. Sp. (trabecular separation), Tb. Pf. (trabecular pattern factor) and SMI (structure model index) by 30.2%, 20.8% and 23.6%, respectively, and a decrease in Tb.N. (trabecular number) index by 18.6%, indicating calcium washout, decreased trabecular connectivity and a transition from a lamellar to a rod-like architecture. Similar changes were found in the 3D-analysis of the jaw bone tissue. Thus, a decrease of 18.9% in mineral density was found, as well as a signiﬁcant increase of 11.58 and 2.21 in the indices, particularly Tb. Pf. and SMI. 3D-analysis of iliac microtomography also indicates a simulation of osteoporosis, as evidenced by a signiﬁcant increase in the main indices characterising the development of this pathology.

Conclusions. The obtained results not only objectively testify to the development of osteoporosis in the experimental animals, but also indicate signs of the adaptation-compensatory reactions of the body, characterized by appearance of large single trabeculae in the metaphysis of the femur as well as by not expressed reduction of bone mineral density and bone tissue area.
TISSUE-ENGINEERED BONE IMPLANTS FOR THE REPLACEMENT OF JAWBONE DEFECTS. LITERATURE REVIEW
Authors: Kobets K. , Kazaryan A. , Bopkhoev S.
Published: September 2022

The purpose of the study:to trace the development of methods of bone implants for the replacement of jawbone defects: from ceramic and polymeric scaffolds to complex tissue-engineered structures with stem cells, growth factors and vascular anastomoses based on literature data.

Materials and methods:searching, systematization and analysis of scientiﬁc data on various types of 3D-printed bone implants and their effectiveness in replacing bone defects.

Conclusions:Modern technologies of 3D-printing, cell and tissue engineering, microvascular surgical techniques closely approach scientists and clinicians to creation of an artiﬁcial bone implant which in the body must become a living structure capable of integrating with the patient’s bone. Only complex approach which includes reconstruction of the implant of individual shape and sufﬁcient mechanical strength, giving of osteoinductive and osteogenic properties, providing of internal axial and external angiogenesis is the basis for such tissue-engineered construction.
THE EFFECT of HIGH-INTENSITY INTERVAL PHYSICAL TRAINING ON THE ENERGY SUPPLY SYSTEM IN PATIENTS AFTER HEART SURGERY
Authors: Kuular A. , Kakuchaya T. , Dzhitava T. , Filatova A. , Pachuashvili N.
Published: September 2022

Introduction. A number of studies have found a reduction in the risk of rehospitalization during cardiorehabilitation after heart surgery. The purpose of the training program for cardiorehabilitation after cardiac surgery is to optimize energy supply systems. Depending on the intensity and duration of the load being performed, energy supply systems 'switch on' in the body.

Purpose of the study: to study the effectiveness of the optimal cardiorehabilitation training program on the aerobic energy supply system in cardiac surgery patients.

Materials and methods. In our study, we examined 47 patients who underwent aortic valve replacement under cardiopulmonary bypass, with an EC duration of 52±20.5 minutes. The patients were divided into two groups: the control group (n=23), who underwent a course of cardiorehabilitation on exercise bikes with constant aerobic training of moderate and medium intensity, at the age of 50.2±3.4 years, and the main group (n=24) – with a course of cardiorehabilitation on exercise bikes with aerobic high-intensity interval physical training, at the age of 51.2±2.8 years (p>0.05). Gender was not taken into account. Anaerobic training was carried out on SCHILLER exercise bikes from day 14 after aortic valve replacement. The load power ranged from 25 to 70–95 watts. Before cardiac rehabilitation, the level of lactate, glucose, pH, pCO2, pO2, BE, lipid proﬁle, BNP in the blood before and after ergometric exercise, data on external respiration, heart rate and blood pressure were assessed. After the course of rehabilitation, the above parameters were evaluated. The duration of the course was 2 weeks. Results. When evaluating the indicators at the end of the course of cardiorehabilitation was being done, a signiﬁcant decrease in the controlled parameters after training was observed in both groups, and largely in the group of high-intensity interval physical training than in the group of constant training of medium intensity.

Conclusions. Analysis of the results showed that properly selected parameters of high-intensity interval training could optimize anaerobic glycolysis in patients undergoing operations under cardiopulmonary bypass, as well as increase the functionality of patients. As more and more repetitions of the load are performed, interval training becomes more and more aerobic.
СПІВВІДНОШЕННЯ НЕГЛАСНИХ СЛІДЧИХ (РОЗШУКОВИХ) ДІЙ З АУДІОКОНТРОЛЮ ОСОБИ ТА АУДІОКОНТРОЛЮ МІСЦЯ
Authors: Моргун І. О. , Богініч І. О. , Артюхова Н. О.
Published: September 2022

У статті розглянуто окремі законодавчі й теоретичні положення щодо негласних слідчих (розшукових) дій з аудіоконтролю особи та аудіоконтролю місця. Основна ува­га приділена розмежуванню цих дій на основі таких критеріїв, як місце проведення дії та наявність або відсутність втручання у приватне спілкування. З’ясовано, що поняття «приватне спілкування» та «втручання у приватне спілкування» (пункти 3, 4 глави 258 Кримінального процесуального кодексу України) по відношенню до аудіоконтролю особи потребують суттєвого уточнення з наведенням вичерпних умов (особливо фізичних), які б чітко вказували на захищеність спілкування від втручання інших осіб. Наразі такими юридичними умовами є гарантовані конституцією недоторканність житла чи іншого володіння особи, а також невтручання в особисте й сімейне життя. Для публічно доступних та публічно недоступних місць гарантією забезпечення приватного спілкування можуть бути тільки фізичні умови (наприклад, достатня відстань від учасників спілкування до сторонніх осіб; низький рівень гучності розмови учасників спілкування тощо), об’єктивність використання яких викликає сумніви. З’ясовано, що аудіоконтроль особи може проводитись у житлі чи іншому володінні особи, у публічно недоступних місцях, а також у публічно доступних місцях, якщо при цьому відбувається втручання у приватне спілкування. Аудіоконтроль місця проводиться ті­льки в публічно доступних місцях за умови, що втручання у приватне спілкування відсутнє. На підставі чинних нормативно-правових актів надано максимально розгорнутий перелік можливих місць для проведення досліджуваних дій. Висунуто пропозицію щодо доцільності об’єднання аудіоконтролю особи та аудіо­контролю місця в одну дію – «аудіоконтроль особи». Вона обґрунтована тим, що аудіоконтроль особи та аудіоконтроль місця мають однаковий об’єкт, яким є певні розмови, інші звуки, рухи, дії певної особи.
ПРОБЛЕМА ВСТАНОВЛЕННЯ ВЗАЄМОЗВ’ЯЗКУ КРИМІНАЛЬНИХ ПРАВОВИХ ТА КРИМІНАЛЬНИХ ПРОЦЕСУАЛЬНИХ НОРМ ПРИ ЗАКОНОДАВЧІЙ РЕГЛАМЕНТАЦІЇ ПІДСТАВ ЗАКРИТТЯ КРИМІНАЛЬНОГО ПРОВАДЖЕННЯ
Authors: Шайтуро О. П.
Published: September 2022

Законодавець при викладенні кримінальних процесуальних норм часто використовує у їх конструкції кримінально-правові категорії, які виконують роль гіпотези та при явності або відсутності яких кримінальна процесуальна норма піддається застосуванню, зокрема й при вирішенні питання щодо наявності підстав для закриття кримінального провадження або його продовження. Проте, як встановлено в результаті дослідження, при регламентації норм кримінального процесу, кримінально-правові категорії далеко не завжди правильно застосовуються законодавцем. На основі кримінально-правового значення таких категорії, як «тяжкий або особливо тяжкий зло­чин про­ти життя чи здоров’я особи» та «строки давності кримінальної відповідальності», встановлені межі їх застосування при конструюванні норм п.п. 3-1, 10 ч.1 ст. 284 КПК України, які регламентують підстави закриття кримінального провадження та можливість його продовження за умови вчинення тяжкого або особливо тяжкого злочину проти життя чи здоров’я особи. У підсумку зазначено про наявність юридичних колізій між нормами кримінального права та кримінального процесу в згаданій частині, які виражаються в невідповідності норм кримінального процесу нормам кримінального права. З метою удосконалення кримінального процесуального законодавства в дослідженій частині, запропоновано внести зміни до Кримінального процесуального кодексу України у п.3-1 ч.1 ст. 284 КК України та в п. 3-1 ч.1 ст. 284 КК України.
ТЕОРЕТИКО-ПРАВОВЕ ОСМИСЛЕННЯ ҐЕНДЕРНОЇ РІВНОСТІ В НАЦІОНАЛЬНІЙ ЮРИДИЧНІЙ ДУМЦІ СЬОГОДЕННЯ
Authors: Maгновський I.Й.
Published: September 2022

У статті висвітлено в теоретико-правовому аспекті сутність та зміст ґендерної рівності, з огляду на дослідження національної юридичної науки. Наголошено, що ґендерна рівність є фундаментальною цінністю, яка лежить у правовій практиці міжнародних стандартів та слугує істотним показником демократичного розвитку громадянського суспільства. Акцентовано увагу на понятті «ґендер» як організованої моделі соціальних взаємин між жінками і чоловіками, що характеризує не лише спілкування в сім’ї, а й визначає їхні соціальні відносини в основних державних інститутах, де онтологічна складова полягає в забезпеченні рівноправності взаємовідносин чоловіка і жінки в соціумі, а принципи рівноправності складають праксеологічний аспект ґендеру. Виокремлено характерні ознаки «ґендеру»: 1) це поняття про систему ролей і відносин між жінками та чоловіками, які детермінуються соціальним, політичним та економічним контекстом і ґрунтуються на умовах конструктивного співробітництва; 2) це взаємодія обох половин статі суспільства, концептуальну основу якої становить безконфліктність і консенсус; 3) «ґендер» передбачає не тільки конструктивну, а й справедливу взаємодію статей по створенню таких соціальних умов, які дають імпульс для розкриття і громадянських, й індивідуальних якостей особистості з метою її повної самореалізації. Ураховано особливості статі, де жінка і чоловік є рівними, але відмінними, і вони рівноправні у своїй несхожості; їхні відмінності – це особливості тієї чи іншої статі, що повинні бути враховані шляхом надання жінкам і чоловікам особливих груп прав і відповідних механізмів реалізації цих прав. Зазначено, що ґендерні відмінності не є перешкодою для рівності, їх існування вимагає диференціації законодавства і відображення в спеціальних нормах. Запропоновано розглядати ґендерну рівність у чотирьох вимірах, які лежать в основі напрямів розвитку державної ґендерної політики: перший – це права людини як стандарт політичних, громадянських, економічних, соціальних і культурних прав і свобод для жінок та чоловіків; другий – це права людини як права жінок; третій – рівність свобод, прав та обов’язків; четвертий – це рівні можливості – основний елемент ґендерної рівності. Підсумовано, що ґендерна рівність являє собою комплексну складову правового статусу жіночої та чоловічої статі з урахуванням їхніх особливостей, забезпечуючи їм рівні можливості участі в суспільно-політичному, соціально-економічному та національно-культурному житті держави й суспільства, створення однакових умов для реалізації прав і свобод, що носить системний характер, а також для власних потреб та розвитку особистого потенціалу, в основі якого покладений рівноправний доступ до певних матеріальних і нематеріальних благ і цінностей.
Machine Gun Politics: Why Politicians Cooperate with Criminal Groups
Authors: Trudeau Jessie
Published: September 2022

Why do politicians cooperate with organized criminal groups? Existing accounts explore such groups’ incentives to cooperate, but largely treat politicians as either victims of violence or passive bribe takers. This paper considers why politicians may seek criminals’ help to get votes. I argue that some politicians win by using an electoral strategy called criminal clientelism. Politicians hire criminal groups as brokers to deliver votes through two mechanisms: (1) corralling mobilizes groups of residents to the polls and (2) gatekeeping prevents rival candidates from accessing voters. I use a natural experiment that leverages exogenous variation in voter assignment to ballot boxes and a novel dataset on criminal governance to test my theory in Rio de Janeiro, Brazil. I show that corralling increases turnout and influences vote choice, and gatekeeping restricts the candidate pool. Together, the mechanisms underpinning criminal clientelism decrease competitiveness and increase the probability of victory for criminally allied candidates.
A light-activated magnetic bead strategy utilized in spatio-temporal controllable exosomes isolation
Authors: Wang Chenhan , Zhang Duoteng , Yang Haiyan , Shi Liang , Li Lin , Yu Changmin , Wei Jifu , Ding Qiang
Published: September 2022

Tumor-derived exosomes are considered as a key biomarker in the field of liquid biopsy. However, conventional separation techniques such as ultracentrifugation, co-precipitation and column chromatography cannot isolate samples with high throughput, while traditional immunomagnetic separation techniques, due to steric effect of magnetic beads, reducing sensitivity of exosomes optical detection. Herein, we provide a novel and simple nanoplatform for spatiotemporally controlling extraction and elution of exosomes via magnetic separation and light-activated cargo release. In this system, magnetic beads are co-modified by photoresponsive groups -nitrobenzyl group and aptamers that are compatible with CD63-a highly expressed exosomal surface-specific protein. Through exosomes extracted from cell model and nude mice xenograft tumor model morphological characterization and proteomic analysis, results showed that our novel magnetic bead system outperformed current ultracentrifugation in serum exosome extraction in terms of extraction time, yield, and proportion of populations with high CD63 expression. This strategy may be a powerful tool for exosome isolation in clinical liquid biopsies of cancer disease.
Oblique impact responses of Hybrid III and a new headform with more biofidelic coefficient of friction and moments of inertia
Authors: Yu Xiancheng , Halldin Peter , Ghajari Mazdak
Published: September 2022

New oblique impact methods for evaluating head injury mitigation effects of helmets are emerging, which mandate measuring both translational and rotational kinematics of the headform. These methods need headforms with biofidelic mass, moments of inertia (MoIs), and coefficient of friction (CoF). To fulfill this need, working group 11 of the European standardization head protection committee (CEN/TC158) has been working on the development of a new headform with realistic MoIs and CoF, based on recent biomechanics research on the human head. In this study, we used a version of this headform (Cellbond) to test a motorcycle helmet under the oblique impact at 8 m/s at five different locations. We also used the Hybrid III headform, which is commonly used in the helmet oblique impact. We tested whether there is a difference between the predictions of the headforms in terms of injury metrics based on head kinematics, including peak translational and rotational acceleration, peak rotational velocity, and BrIC (brain injury criterion). We also used the Imperial College finite element model of the human head to predict the strain and strain rate across the brain and tested whether there is a difference between the headforms in terms of the predicted strain and strain rate. We found that the Cellbond headform produced similar or higher peak translational accelerations depending on the impact location (−3.2% in the front-side impact to 24.3% in the rear impact). The Cellbond headform, however, produced significantly lower peak rotational acceleration (−41.8% in a rear impact to −62.7% in a side impact), peak rotational velocity (−29.5% in a side impact to −47.6% in a rear impact), and BrIC (−29% in a rear-side impact to −45.3% in a rear impact). The 90th percentile values of the maximum brain strain and strain rate were also significantly lower using this headform. Our results suggest that MoIs and CoF have significant effects on headform rotational kinematics, and consequently brain deformation, during the helmeted oblique impact. Future helmet standards and rating methods should use headforms with realistic MoIs and CoF (e.g., the Cellbond headform) to ensure more accurate representation of the head in laboratory impact tests.
Recent advancement of bioinspired nanomaterials and their applications: A review
Authors: Wu Gang , Hui Xiaodan , Hu Linhui , Bai Yunpeng , Rahaman Abdul , Yang Xing-Fen , Chen Chunbo
Published: September 2022

With the advancement in the field of nanotechnology, different approaches for the synthesis of nanomaterials have been formulated, among which the bioinspired or biomimetic nanoplatforms have been utilized for different biomedical applications. In this context, bioinspired or biomimetic nanoparticles (NPs) have been synthesized in which the inspiration for synthesis is taken from nature or its components. Innovations in bioengineering tools and bio-conjugation chemistry have enabled scientists to develop novel types of such nanoplatforms. They have several advantages over normal synthesis protocols. In this review, we 1) summarized nanomaterial types and their advancements in bioinspired nanotechnology therapies; 2) discussed the major types, novel preparation methods, and synthesis progress of NPs in current biomedical fields; 3) gave a brief account of the need for synthesizing NPs via a bioinspired route rather than their common route; 4) highlighted the updated information on the biomimetic synthesis of different types of NPs; and 5) provided future perspectives in the synthesis of novel NPs for their potential applications in biomedical sciences.
Biomechanical comparison between unilateral and bilateral percutaneous vertebroplasty for osteoporotic vertebral compression fractures: A finite element analysis
Authors: Dai Haowen , Liu Yang , Han Qing , Zhang Aobo , Chen Hao , Qu Yang , Wang Jincheng , Zhao Jianwu
Published: September 2022

Background and objective: The osteoporotic vertebral compression fracture (OVCF) has an incidence of 7.8/1000 person-years at 55–65 years. At 75 years or older, the incidence increases to 19.6/1000 person-years in females and 5.2–9.3/1000 person-years in males. To solve this problem, percutaneous vertebroplasty (PVP) was developed in recent years and has been widely used in clinical practice to treat OVCF. Are the clinical effects of unilateral percutaneous vertebroplasty (UPVP) and bilateral percutaneous vertebroplasty (BPVP) the same? The purpose of this study was to compare biomechanical differences between UPVP and BPVP using finite element analysis.

Materials and methods: The heterogeneous assignment finite element (FE) model of T11-L1 was constructed and validated. A compression fracture of the vertebral body was performed at T12. UPVP and BPVP were simulated by the difference in the distribution of bone cement in T12. Stress distributions and maximum von Mises stresses of vertebrae and intervertebral discs were compared. The rate of change of maximum displacement between UPVP and BPVP was evaluated.

Results: There were no obvious high-stress concentration regions on the anterior and middle columns of the T12 vertebral body in BPVP. Compared with UPVP, the maximum stress on T11 in BPVP was lower under left/right lateral bending, and the maximum stress on L1 was lower under all loading conditions. For the T12-L1 intervertebral disc, the maximum stress of BPVP was less than that of UPVP. The maximum displacement of T12 after BPVP was less than that after UPVP under the six loading conditions.

Conclusion: BPVP could balance the stress of the vertebral body, reduce the maximum stress of the intervertebral disc, and offer advantages in terms of stability compared with UPVP. In summary, BPVP could reduce the incidence of postoperative complications and provide promising clinical effects for patients.
Easily automated radiosynthesis of [18F]P10A-1910 and its clinical translation to quantify phosphodiesterase 10A in human brain
Authors: Wei Huiyi , Wei Junjie , Zhang Shaojuan , Dong Shiliang , Li Guocong , Ran Wenqing , Dong Chenchen , Zhang Weibin , Che Chao , Luo Wenzhao , Xu Hao , Dong Zhiyong , Wang Jinghao , Wang Lu
Published: September 2022

Our previous work showed that [18F]P10A-1910 was a potential radioligand for use in imaging phosphodiesterase 10A (PDE10A). Specifically, it had high brain penetration and specific binding that was demonstrated in both rodents and non-human primates. Here, we present the first automatic cGMP-level production of [18F]P10A-1910 and translational PET/MRI study in living human brains. Successful one-step radiolabeling of [18F]P10A-1910 on a GE TRACERlab FX2N synthesis module was realized via two different methods. First, formulated [18F]P10A-1910 was derived from heating spirocyclic iodonium ylide in a tetra-n-butyl ammonium methanesulfonate solution. At the end of synthesis, it was obtained in non-decay corrected radiochemical yields (n.d.c. RCYs) of 12.4 ± 1.3%, with molar activities (MAs) of 90.3 ± 12.6 μmol (n = 7) (Method I). The boronic pinacol ester combined with copper and oxygen also delivered the radioligand with 16.8 ± 1.0% n. d.c. RCYs and 77.3 ± 20.7 GBq/μmol (n = 7) MAs after formulation (Method II). The radiochemical purity, radionuclidic purity, solvent residue, sterility, endotoxin content and other parameters were all validated for human use. Consistent with the distribution of PDE10A in the brain, escalating uptake of [18F]P10A-1910 was observed in the order of cerebellum (reference region), substantial nigra, caudate and putamen. The non-displaceable binding potential (BPND) was estimated by simplified reference-tissue model (SRTM); linear regressions demonstrated that BPND was well correlated with the most widely used semiquantitative parameter SUV. The strongest correlation was observed with SUV(50–60 min) (R2 = 0.966, p < 0.01). Collectively, these results indicated that a static scan protocol could be easily performed for PET imaging of PDE10A. Most importantly, that [18F]P10A-1910 is a promising radioligand to clinically quantify PDE10A.
MFN2 mediates ER-mitochondrial coupling during ER stress through specialized stable contact sites
Authors: Gottschalk Benjamin , Koshenov Zhanat , Bachkoenig Olaf A. , Rost René , Malli Roland , Graier Wolfgang F.
Published: September 2022

Endoplasmic reticulum (ER) functions critically depend on a suitable ATP supply to fuel ER chaperons and protein trafficking. A disruption of the ability of the ER to traffic and fold proteins leads to ER stress and the unfolded protein response (UPR). Using structured illumination super-resolution microscopy, we revealed increased stability and lifetime of mitochondrial associated ER membranes (MAM) during ER stress. The consequent increase of basal mitochondrial Ca2+ leads to increased TCA cycle activity and enhanced mitochondrial membrane potential, OXPHOS, and ATP generation during ER stress. Subsequently, OXPHOS derived ATP trafficking towards the ER was increased. We found that the increased lifetime and stability of MAMs during ER stress depended on the mitochondrial fusion protein Mitofusin2 (MFN2). Knockdown of MFN2 blunted mitochondrial Ca2+ effect during ER stress, switched mitochondrial F1FO-ATPase activity into reverse mode, and strongly reduced the ATP supply for the ER during ER stress. These findings suggest a critical role of MFN2-dependent MAM stability and lifetime during ER stress to compensate UPR by strengthening ER ATP supply by the mitochondria.
Chronic unpredictable mild stress-induced mouse ovarian insufficiency by interrupting lipid homeostasis in the ovary
Authors: Xiang Yongjie , Jiang Lin , Gou Junjie , Sun Yibo , Zhang Dongyu , Xin Xigeng , Song Zhenhua , Huang Jiaojiao
Published: September 2022

Ovarian insufficiency results from a number of disorders, and a certain causal relationship between psychological stress and ovarian insufficiency has been reported, but the underlying mechanism remains unclear. In our study, C57BL/6J female mice were subjected to chronic unpredictable mild stress (CUMS), and depression-like mice were selected and identified according to the behavioral tests. The defective ovarian follicle development, low 17 β-estradiol (E2), and anti-Mullerian hormone (AMH) levels, which were consistent with the clinical characteristics of ovarian insufficiency, indicated that depression-like mice may be used to assess the effects of psychological stress on female reproductive function. To investigate a possible mechanism, lipid homeostasis of the ovary was detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, and the decreased abundance of cholesteryl ester (CE 24:4) was supported to be associated with the downregulated E2. Moreover, granulosa cells did undergo more apoptosis in response to psychological stress, which was caused by downregulated Bcl2 and Bcl2/Bax in granulosa cells. Additionally, the disorder of cell death and growth-related pathways in depression-like mouse ovaries was confirmed by RNA-seq analysis. Taken together, this study will provide a better understanding of the female reproductive problem under psychological stress.
Super-enhancer associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells
Authors: Gomez Roshna Lawrence , Woods Laura M. , Ramachandran Revathy , Abou Tayoun Ahmad N. , Philpott Anna , Ali Fahad R.
Published: September 2022

Neuroblastoma is a pediatric tumour that accounts for more than 15% of cancer-related deaths in children. High-risk tumours are often difficult to treat, and patients’ survival chances are less than 50%. Retinoic acid treatment is part of the maintenance therapy given to neuroblastoma patients; however, not all tumours differentiate in response to retinoic acid. Within neuroblastoma tumors, two phenotypically distinct cell types have been identified based on their super-enhancer landscape and transcriptional core regulatory circuitries: adrenergic (ADRN) and mesenchymal (MES). We hypothesized that the distinct super-enhancers in these different tumour cells mediate differential response to retinoic acid. To this end, three different neuroblastoma cell lines, ADRN (MYCN amplified and non-amplified) and MES cells, were treated with retinoic acid, and changes in the super-enhancer landscape upon treatment and after subsequent removal of retinoic acid was studied. Using ChIP-seq for the active histone mark H3K27ac, paired with RNA-seq, we compared the super-enhancer landscape in cells that undergo neuronal differentiation in response to retinoic acid versus those that fail to differentiate and identified unique super-enhancers associated with neuronal differentiation. Among the ADRN cells that respond to treatment, MYCN-amplified cells remain differentiated upon removal of retinoic acid, whereas MYCN non-amplified cells revert to an undifferentiated state, allowing for the identification of super-enhancers responsible for maintaining differentiation. This study identifies key super-enhancers that are crucial for retinoic acid-mediated differentiation.
Direct modulation of microglial function by electrical field
Authors: Lennikov Anton , Yang Menglu , Chang Karen , Pan Li , Saddala Madhu Sudhana , Lee Cherin , Ashok Ajay , Cho Kin-Sang , Utheim Tor Paaske , Chen Dong Feng
Published: September 2022

Non-invasive electric stimulation (ES) employing a low-intensity electric current presents a potential therapeutic modality that can be applied for treating retinal and brain neurodegenerative disorders. As neurons are known to respond directly to ES, the effects of ES on glia cells are poorly studied. A key question is if ES directly mediates microglial function or modulates their activity merely via neuron-glial signaling. Here, we demonstrated the direct effects of ES on microglia in the BV-2 cells—an immortalized murine microglial cell line. The low current ES in a biphasic ramp waveform, but not that of rectangular or sine waveforms, significantly suppressed the motility and migration of BV-2 microglia in culture without causing cytotoxicity. This was associated with diminished cytoskeleton reorganization and microvilli formation in BV-2 cultures, as demonstrated by immunostaining of cytoskeletal proteins, F-actin and β-tubulin, and scanning electron microscopy. Moreover, ES of a ramp waveform reduced microglial phagocytosis of fluorescent zymosan particles and suppressed lipopolysaccharide (LPS)-induced pro-inflammatory cytokine expression in BV-2 cells as shown by Proteome Profiler Mouse Cytokine Array. The results of quantitative PCR and immunostaining for cyclooxygenase-2, Interleukin 6, and Tumor Necrosis Factor-α corroborated the direct suppression of LPS-induced microglial responses by a ramp ES. Transcriptome profiling further demonstrated that ramp ES effectively suppressed nearly half of the LPS-induced genes, primarily relating to cellular motility, energy metabolism, and calcium signaling. Our results reveal a direct modulatory effect of ES on previously thought electrically “non-responsive” microglia and suggest a new avenue of employing ES for anti-inflammatory therapy.
Chemistries and applications of DNA-natural product conjugate
Authors: Chen Yuanyuan , Li Wenting , Xing Hang
Published: September 2022

Natural products and their derivatives have made great contributions to chemotherapy, especially for the treatment of tumors and infections. Despite the achievements, natural product-based small molecule drugs usually suffer from side effects, short circulation time, and solubility issue. To overcome these drawbacks, a common approach is to integrate another bio-functional motif into a natural product compound, enabling targeted or synergistic therapy. One of the most promising strategies is to form a DNA-natural product conjugate to improve therapeutic purposes. The incorporated DNA molecules can serve as an aptamer, a nucleic-acid-based congener of antibody, to specifically bind to the disease target of interest, or function as a gene therapy agent, such as immuno-adjuvant or antisense, to enable synergistic chemo-gene therapy. DNA-natural product conjugate can also be incorporated into other DNA nanostructures to improve the administration and delivery of drugs. This minireview aims to provide the chemistry community with a brief overview on this emerging topic of DNA-natural product conjugates for advanced therapeutics. The basic concepts to use the conjugation, the commonly used robust conjugation chemistries, as well as applications in targeted therapy and synergistic therapy of using DNA-natural product conjugates, are highlighted in this minireview. Future perspectives and challenges of this field are also discussed in the discussion and perspective section.
Maturation of subtilisin-like protease NbSLP1 from microsporidia Nosema bombycis
Authors: Wang Rong , Li Qingyan , Liu Fangyan , Dang Xiaoqun , Sun Quan , Sheng Xiaotian , Hu Mingyu , Bao Jialing , Chen Jie , Pan Guoqing , Zhou Zeyang
Published: September 2022

Microsporidia are obligate intracellular parasites and possess a unique way of invading hosts, namely germination. Microsporidia are able to infect almost all animal cells by germination. During the process, the polar tube extrudes from the spores within, thus injecting infectious sporoplasm into the host cells. Previous studies indicated that subtilisin-like protease 1 (NbSLP1) of microsporidia Nosema bombycis were located at the polar cap of germinated spores where the polar tube extrusion. We hypothesized that NbSLP1 is an essential player in the germination process. Normally, SLP need to be activated by autoproteolysis under conditions. In this study, we found that the signal peptide of NbSLP1 affected the activation of protease, two self-cleavage sites were involved in NbSLP1 maturation between Ala104Asp105 and Ala124Asp125 respectively. Mutants at catalytic triad of NbSLP1 confirmed the decreasing of autoproteolysis. This study demonstrates that intramolecular proteolysis is required for NbSLP1 maturation. The protease undergoes a series of sequential N-terminal cleavage events to generate the mature enzyme. Like other subtilisin-like enzymes, catalytic triad of NbSLP1 are significant for the self-activation of NbSLP1. In conclusion, clarifying the maturation of NbSLP1 will be valuable for understanding the polar tube ejection mechanism of germination.
Multidisciplinary engagement for fencing research informs efficacy and rancher-to-researcher knowledge exchange
Authors: Hyde Matthew , Breck Stewart W. , Few Alex , Beaver Jared , Schrecengost Joshua , Stone Jim , Krebs Cameron , Talmo Russell , Eneas Kari , Nickerson Rae , Kunkel Kyran E. , Young Julie K.
Published: September 2022

Across much of the Western United States, recovery of large carnivore populations is creating new challenges for livestock producers. Reducing the risks of sharing the landscape with recovering wildlife populations is critical to private working lands, which play an vital role in securing future energy, water, food, and fiber for an ever-expanding human population. Fencing is an important mitigation practice that many ranchers, land managers, and conservationists implement to reduce carnivore-livestock conflict. While fencing strategies have been reviewed in the literature, research seldom incorporates knowledge from the people who utilize fencing the most (i.e., livestock producers). Incorporating producers and practitioners early in the process of producing scientific knowledge is proving to be a critical endeavor for enhancing knowledge exchange, better evaluation of the practice, and more realistic understanding of the costs and benefits. Here, we describe how our multidisciplinary effort of co-producing knowledge informs understanding of the effectiveness of various fencing designs and more importantly provides a better mechanism for transferring this knowledge between producers, researchers, and land managers. We explain the process underway and demonstrate that incorporating producers and practitioners from the onset allows research priorities and expected outcomes to be set collaboratively, gives transparency to the agricultural community of the research process, provides a critical lens to evaluate efficacy and functionality, and will inform the practicality of fencing as a conflict prevention tool. We discuss opportunities and challenges of this co-production process and how it can be applied to other realms of fencing and conflict prevention strategies.
Higher neutrophil to lymphocyte ratio is associated with renal dysfunction and cardiac adverse remodeling in elderly with metabolic syndrome
Authors: Zhu Yuqi , Li Gang , Laukkanen Jari A. , Song Xing , Zhang Jing , Wei Linping , Chen Xinrui , Li Yufeng , Liu Cheng
Published: September 2022

Background

Previous studies have shown that metabolic syndrome (MetS) is associated with increased systemic inflammation and cardiac mortality in elderly subjects. However, information on the association of inflammation markers with cardiac adverse remodeling is limited in the elderly with MetS. Therefore, we investigated whether the inflammatory marker neutrophil/lymphocyte ratio (NLR) is associated with the cardiac adverse remodeling in Chinese elderly with MetS.

Methods

A total of 1,087 hospitalized Chinese elderly (aged ≥ 65 years) with MetS were collected retrospectively. The cross-sectional data of echocardiography and clinical parameters were compared among quartile NLR groups.

Results

In the elderly with MetS, higher quartile NLR (≥3.83) was found to be associated with male gender, older age, lower estimated glomerular filtration rate (eGFR), and cardiac left ventricular (LV) dilatation (all p <0.05).

Conclusion

Higher NLR is associated with male gender, older age, renal dysfunction, and cardiac adverse remodeling in Chinese elderly with MetS.
Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms
Authors: Chen Yubin , Ouyang Tianyu , Fang Cheng , Tang Can-e , Lei Kaibo , Jiang Longtan , Luo Fanyan
Published: September 2022

Objectives

The mortality rate of abdominal aortic aneurysm (AAA) is extremely high in the older population. This study aimed to identify potential biomarkers of AAA and aortic rupture and analyze infiltration of immune cells in stable and ruptured AAA samples.

Methods

Raw data of GSE47472, GSE57691, and GSE98278 were downloaded. After data processing, the co-expression gene networks were constructed. Gene Ontology and pathway enrichment analysis of AAA- and aortic rupture-related gene modules were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for further enrichment analysis. The CIBERSORT tool was used to analyze the relative abundance of immune cells in samples. Differentially expressed immune-related genes were analyzed between different samples. Predictive models were constructed via extreme gradient boosting, and hub genes were identified according to feature importance.

Results

Blue and yellow modules were significantly related to AAA, and genes in these modules were associated with the aortic wall and immune response, respectively. In terms of aortic rupture, the most relevant module was significantly enriched in the inflammatory response. The results of GSEA and GSVA suggested that immune cells and the inflammatory response were involved in the development of AAA and aortic rupture. There were significant differences in the infiltration of immune cells and expression levels of immune-related genes among different samples. NFKB1 might be an important transcription factor mediating the inflammatory response of AAA and aortic rupture. After the construction of a predictive model, CD19, SELL, and CCR7 were selected as hub genes for AAA whereas OAS3, IFIT1, and IFI44L were identified as hub genes for aortic rupture.

Conclusion

Weakening of the aortic wall and the immune response both contributed to the development of AAA, and the inflammatory response was closely associated with aortic rupture. The infiltration of immune cells was significantly different between different samples. NFKB1 might be an important transcription factor in AAA and aortic rupture. CD19, SELL, and CCR7 had potential diagnostic value for AAA. OAS3, IFIT1, and IFI44L might be predictive factors for aortic rupture.