bluuebunny/crossref_metadata_2025 huggingface dataset:
CRONY CAPITALIM AND STYMIED DEVELOPMENT IN SOUTH AFRICA AND ZIMBABWE: Cry the Beloved Countries
Authors: Karodia Anis Mahomed , Soni Paresh , Thomas Stanton
Published: October 2021

Crony capitalism is the precursor to many of the woes of any country. It makes the rich richer and lessens the participation of the poor in the economy of any country, and thus automatically makes them poorer. This paper therefore, looks at crony capitalism from a South African viewpoint, in order to place into perspective the issues of development that are seriously compromised. In so doing the paper will attempt to look at some issues that affect development because of the scourge of crony capitalism. It would therefore, discuss the hidden billions of South Africa’s elite, which hampers progress and development, ushers in strikes and thus compromises stability and the economic balance of the country. That the billions of rands earned by chief executives could be used to promote and advance the issues of development, bring about stability in all sectors of the economy and, particularly in the mining sector of South Africa and issues that confront the poor. The paper expands the discussion by asking the question – Is South Africa’s left on the right road to socialism? It therefore explores the allegiance to Marxist – Leninism and statism and argues that that they are out of step with modern democratic practice. The paper also exemplifies the problems that confront Zimbabwe, in terms of its debt crisis due to overt cronyism and shows that Zimbabwe is at the crossroads of development with increasing poverty, unemployment and inequality, and is drowning in debt. It argues that it is crunch time for President Robert Mugabe and his ZANU political party.
FINANCING SMALL AND MEDIUM SCALE BUSINESS IN AFRICAN COUNTRIES: PROBLEMS AND PROSPECTS
Authors: Ene Emeka E. , Ene Josephine C.
Published: October 2021

Access to finance has been noted as one of the major challenges impeding the survival and growth of the SME sector in most of African countries. This review paper provides a comprehensive discussion on access to finance by the Small and Medium Enterprises (SME) sector in African countries. The problems of access to finance, gaps and the reasons for the gaps in SME financing in African countries are discussed. Gaps in SME financing were discussed in relation to Stiglitz and Weiss (1981) credit rationing theory which advocates that agency problems and asymmetric information are the main reasons for the credit rationing behaviors of credit providers to SMEs. The paper reveals that access to finance by SMEs is still a major challenge impeding the realization of the full potential of SMEs as engines of poverty alleviation, employment creation and economic growth in Africa. Therefore it is recommended that policy efforts aimed at solving access to finance challenges must be monitored and empirically tested on a regular basis to enable informed policy thrusts that would enhance SMEs access to financing.
AN EMPIRICAL STUDY OF FACTORS AFFECTING THE EFFECTIVENESS OF INTERNATIONAL AIDS IN THE NIGER DELTA RURAL COMMUNITIES
Authors: Akpojaro Jackson , Ihesiene Chukwuemeka Ugwu
Published: October 2021

In this paper, we examine the key factors inhibiting effective delivery of international donor-aided interventions in the Niger Delta rural communities from the beneficiaries. We review current intervention issues and challenges with a view to recommending deliberate steps towards ensuring effectiveness in implementation. This study captures survey data from 70 randomly selected rural projects located in the Niger Delta region. The simple percentages, Analysis of Variance and Chi-Square were used in the statistical analysis to predict factors challenging intervention effectiveness by measures of: human capacity deficiency, defective delivery framework, corruption, environmental, policy, and funding problems. The research result identifies defective delivery framework as the most inhibiting factor against effective use of aid in rural communities. Other critical factors in their descending order of gravity include funding, corruption, human capacity, policy and environmental problems. Stakeholders should take urgent steps towards dealing with these factors which inhibit effective intervention delivery through beneficiary-based intervention framework, frantic war against corrupt practices, integration of monitoring and evaluation units (MEU) of local governments, alignment of interventions to national development plan, maintenance of intervention databases to reduce duplication of efforts, and establishment of aid management offices (AMOs) at all levels of government. Therefore, this paper is relevant and of interest to international donor agencies, researchers, policy makers, beneficiaries and other stakeholders of sustainable rural development.
A QUALITATIVE APPROACH TO EXPLORE THE ROLE OF INTELLECTUAL CAPITAL PRACTICES (ICP) FOR BANKS’ PERFORMANCES: A Knowledge Base Perspective
Authors: Rehman Wasim ul , Rehman Sumaira , Rehman Abdul
Published: October 2021

This research study has twofold objectives, first to explore in depth knowledge base view of banks’ professionals regarding the adoption of intellectual capital practices (i.e. human capital, structural capital and relational capital) and second to get know professionals subjective opinions about importance of such practices to obtain sustainable performances of banks in a competitive environment. Based on interpretive phenomenological approach (IPA) the study provides multidimensional realistic implications for top management echelons in banking industry and for future academic researchers. The findings of study reveals that intellectual capital practices are deeply addressed by banks’ professionals. Banks are penetrating regarding the human capital (HC), structural capital (SC) and relational capital (RC) practices to build competitiveness through market share and profitability. Learning and education, employee’s experience and expertise and their innovative and creative abilities are very key constructs of human capital. The study explores fore-mentioned abilities provide substantial contribution for banks’ performance in the shape of market share and profitability. The study presents the subjective opinion of twelve participants from a geographical area (Lahore) however more sample size will provide the parsimonious picture about IC awareness and its implementations to link it with banks’ performances.
MEASURING THE QUALITY OF DELIVERY OF SERVICES BASED ON SERVQUAL AND GRONROOS SERVICE QUALITY MODEL CASE STUDY: OSVE SMART ELEMENTARY SCHOOL
Authors: Ghaleh Faezeh Rezaei , Ghaleh Homa Rezaei , Sadati Seyd Ebrahim
Published: October 2021

Measuring is the key element in efficiency cycle and acts as the control system for the other elements of the operating cycle, on the other hand service quality is a very important success in educational organizations. The main objective of this study was to assess the level of quality of service in Osve Smart School in the scale of SERVQUAL and Gronroos service quality model the functional quality of Gronroos model. The population of this research includes smart school parents and students (103) and the statistical sample size is 88 people. By implementing a combination of SERVQUAL and Gronroos standard questionnaire and its reliability in expectations dimension is 0.972 and in perception dimension is 0.967. The results showed that the level of each of the models used; (functional quality, technical quality and image) perceived image quality is in the first place and the functional and technical quality are in the second and third place. Estimates of the overall results suggest that the negative gap between the expectations and perceptions of all sizes, shows that the quality of services in Osve smart school, is not consistent with the expectations of parents.
THE QUALITY OF TRAINING PROGRAMMES AND LEADERSHIP COMPETENCIES AMONG EDUCATIONAL MANAGERS IN THE SULTANATE OF OMAN
Authors: Juma Alarimy Aisha Salim , Othman Azam , Ali Hairuddin Mohd , Ahmad Ismail Sheikh
Published: October 2021

This study examined the quality of training programmes and leadership competencies among educational managers in the Ministry of Education (MoE), Sultanate of Oman. The study examined two objectives which included; (a) to determine the leadership competencies acquired through training among educational managers in MoE, Sultanate of Oman, and (b) to investigate significant differences between leadership competencies among educational managers’ at the MoE Head Quarter and Regional Directorate in the MoE, Sultanate of Oman. A sample of two hundred and ninety eight (298) educational managers in the MoE in the Sultanate of Oman participated in the study. A quantitative approach to research using the Alaraimy Competency Survey as the instrument of data collection was used to conduct the study. The data was analysed using a Confirmatory Factor Analysis (CFA) and MANOVA analyses. The results of the study highlighted that the educational managers possessed all leadership competences, though at different levels. It was also revealed that there were no significant differences in the competence levels between educational managers working at the Headquarter of MoE and those in the Regional General Directorates. It is recommended that the MoE, Sultanate of Oman adopts the best training approaches that develop all the competences of educational managers in the MoE, Sultanate of Oman, both at the MoE Head Quarters and Regional General Directorates.
ODONTOLOGIA NA ERA DA COVID-19: UMA REVISÃO INTEGRATIVA DA LITERATURA
Authors: Santos Raquel Rodrigues , Castro Gabriella Bigossi de , Soares Gabriella Barreto , Sarmento Rosanne Feitosa e Souza
Published: October 2021

A epidemia de COVID-19 foi elevada ao status de pandemia em março de 2020 pela OMS e estende-se até o momento atual em 2021. Os cuidados para mitigação da disseminação de doenças através de medidas de biossegurança já estavam presentes na Odontologia, mas foram redobrados durante a pandemia. O objetivo do estudo foi revisar a literatura acerca da biossegurança na Odontologia durante a pandemia e identificar abordagens para minimização do risco de infecção por SARS-CoV-2. Trata-se de revisão integrativa da literatura através das bases de dados PubMed e Biblioteca Virtual em Saúde (BVS) que utilizou os descritores combinados: (“coronavirus” OR “covid-19”) AND “dentistry” AND (“containment of biohazards” OR “aerosols”). Foram coletados artigos publicados entre 2020 e 2021 e critérios de inclusão e exclusão foram estabelecidos. Dos 29 artigos selecionados, 18 trouxeram como temática central os aerossóis odontológicos, 8 abordaram protocolos e experiências globais frente à pandemia de COVID-19 e 2, medidas de proteção e equipamentos de proteção individual. Observou-se uma preocupação geral em todos os artigos com os riscos oferecidos no ambiente odontológico para a propagação de patógenos, em especial, o SARS-CoV-2, devido à intensa produção de aerossóis que ocorre na maioria dos procedimentos realizados no dia-a-dia da equipe de saúde bucal. Medidas que promovam a redução desse risco estão sendo propostas. O estudo ressalta a necessidade de novas abordagens em odontologia com foco na prevenção do agravamento do número de casos de doenças de forma que haja promoção de saúde bucal através de procedimentos livres de aerossóis.
Association of Restless Leg Syndrome with Iron Deficiency Anaemia
Authors: Rehman Mujeeb-ul- , Mujtaba Ghulam , Ahmed Zuhaib , Shah Shahnaz , Qararo Shah Syed , Ali Aijaz
Published: October 2021

Background: Iron deficiency anaemia (IDA) and rest leg syndrome (RLS) are two common medical conditions in our population. There is etiologic association between the two pathologies which however; has not been investigated in our local population. Objective: To determine the frequency of iron deficiency anemia among patients of restless leg syndrome. Study Design: Cross sectional study. Place and Duration of Study: Department of Neurology, Khairpur Medical College- Khairpur Mir’s from December 2020 to March 2021. Methodology: Three hundred and thirty nine patients having RLS, of either gender, age 18-60 years, were included after taking a valid informed/written consent. Pregnant women or having menorrhagia, blood dyscrasias, iron supplements or steroids, any neurological comorbid or comatose patients were excluded. Results: The mean age was 39.12±10.79 years. The mean duration of RLS was 8.42±4.01 years while mean haemoglobin was 12.06±2.36 g/dL. The prevalence of IDA among RLS patients was 133 (39.2%). The stratified analysis significantly revealed that elder age, female gender, positive family history, and higher BMI were associated with increased frequency and severity of IDA among RLS patients (P=0.996, 0.007, 0.372 &0.738). Conclusion: Iron deficiency anaemia is quite frequent in patients of Restless leg syndrome and healthcare providers should increase awareness among population regarding its treatment. Key words: Restless leg syndrome, Iron deficiency, Anaemia, Haemoglobin, Sleep disturbance
IN VIVO ASSESSMENT OF BIOAVAILABILITY OF SUSTAINED RELEASE MATRIX TABLETS OF AN ANTIHYPERTENSIVE DRUG IN RABBITS USING REVERSE PHASE CHROMATOGRAPHY
Authors: Pawar H. A , Lalitha K. G. ,   Department of Quality Assurance, Dr. L. H. Hiranandani College of Pharmacy, Smt. CHM Campus, Opp. Ulhasnagar Railway Station, Ulhasnagar - 421 003, Maharashtra, India.
Published: October 2021

A new reverse phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for determination of losartan potassium in rabbit plasma. The calibration curve was linear in the concentration range of 0.025 μg/mL to 0.5 μg/mL with a lower limit of detection at 0.025μg/mL. In addition, stability studies of losartan Potassium in rabbit plasma demonstrated its good stability at − 70°C and at room temperature. The validated method was successfully employed for the estimation of losartan potassium in rabbit plasma following oral administrations of immediate release tablets and sustained release matrix tablets to rabbits. The pharmacokinetic parameters including AUC0–t, AUC0–∞, Cmax, Tmax, T1/2, and elimination rate constant (Kel) were determined from plasma concentration for both the formulations. The absorption and bioavailability of drug from the sustained release tablets was found significantly higher as compared to the reference losartan potassium immediate release tablets because of longer half-life and lower elimination.
ISOLATION AND IDENTIFICATION OF POLYPHENOLIC COMPOUND FROM IPOMOEA AQUATICA FORSK. (CONVOLVULACEAE)
Authors: Manvar M. N , Desai T. R. ,   School of Pharmacy, RK University, Rajkot-Bhavnagar Highway, Kasturbadham, Rajkot - 360 005, Gujarat, India.
Published: October 2021

Ipomoea aquatica is used in Indian system of medicine and many pharmacological activities have been attributed to it. The preliminary phytochemical screening revealed presence of polyphenolic compounds in it. The hydroalcoholic extracts of leaves of Ipomoea aquatica was studied for isolation of flavonoid by chromatographic method. On the basis of study of physical properties, chemical tests and spectroscopic evaluation (UV, IR, 1HNMR and Mass Spectrometry) the structure of the isolated compound was established. The isolated compound was yellow colored and soluble in methanol, ethanol and dimethyl sulfoxide, having melting point range 315-317oC. Interpretations of all the spectra revealed that the isolated compound was quercetin. Thus it was concluded that many pharmacological activities reported on this plant may due to presence of quercetin.
SOME NEW 1,3,4-OXADIAZOLES AS ANTIMICROBIAL AGENTS
Authors: Laddi U. V , Desai S. ,   Department of Chemistry, Channabasaveshwar Institute of Technology, Gubbi - 572 216, Karnataka, India.
Published: October 2021

Some new 5-[(((α-phenyl/methyl)benzylidene)amino)oxy]methyl/ethyl-2-amino/4-substituted aryl/ aryloxymethylarmercapto/piperidino/ morpholino-1,3,4-oxadiazoles (2a-d–5a-d) with biologically active biostere methyelne amino oxy methyl/ethyl moiety, were prepared starting from α/β-[((α-(phenyl/methyl) benzylidene)amino)oxy acetic/propionic acid hydrazides (1a-d). The structures of the compounds have been characterised by elemental and spectral (IR, 1HNMR and mass) analysis. All the newly synthesised compounds have been screened for their antimicrobial activity by cup plate method, against Escherichia coli, Bacillus cirroflagellosus, Aspergillus niger and Rhizoctonia bataticola. Some of the newly synthesised compounds have been evaluated for antituberculosis activity against, Mycobacterium tuberculosis H37Rv strain as well by BACTEC radiometric system at Southern Research Institute and Frederick Research Centre, Frederick, MD.
DESIGN AND EVALUATION OF ROSUVASTATIN SMEDDS FOR ENHANCING SOLUBILITY AND DISSOLUTION RATE
Authors: Vidyadhara S , Sasidhar RLC , Chowdary Y.A , Lavanya K.L. , Lakshmi S. B ,   Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chandarmoulipuram, Chowdavaram, Guntur - 522 019, Andhra Pradesh, India.
Published: October 2021

The objective of present study was to improve solubility and dissolution rate of rosuvastatin by formulating it as a self micro emulsifying drug delivery system (SMEDDS). The SMEDDS were prepared by using capmul McM and capryol 90 as oils Polaxomer 407 as surfactant and Transcutol hP and Soluphor P as co-surfactants. The liquid SMEDDS were then converted into free flowing powder by adsorbing onto solid carriers like magnesium aluminium silicate. The prepared SMEDDs were further evaluated for particle size, phase separation, droplet size, drug content and for in vitro drug release. From the results, it was observed that the SMEDDs were found to be stable. Among the prepared SMEDDS the formulations prepared with oil to co-surfactant ratios of 1:3 showed highest rates of dissolution. The FTIR and DSc analysis on optimised formulations revealed that there were no major interactions between drug and excipients.
FABRICATION AND CHARACTERIZATION OF ZALTOPROFEN LOADED LYOTROPIC LIQUID CRYSTALLINE GEL
Authors: Pande V. , Nayak S. , Kendre P , Patil P , Sagar K. ,   School of Pharmacy, RK University, Rajkot-Bhavnagar Highway, Kasturbadham, Rajkot - 360 005, Gujarat, India.
Published: October 2021

In recent years, most of the non-steroidal anti-inflammatory drugs (NSAID’s) have been designed to deliver the drug in the form of topical gels, to avoid GIT irritation and to maximize drug concentration at the site of action. Liquid crystal phase has emerged as a novel material for the preparation of topical drug delivery system. For the preparation of liquid crystals, we have selected glycerol monooleate (GmO) because it is biocompatible, bioadhesive, a penetration enhancer and sustained release agent. It was proposed to develop zaltoprofen loaded lyotropic liquid crystalline gel. The optimized formulation of this system shows hexagonal phase identified by polarized microscopy and transmission electron microscopy. In vitro drug release kinetics shows that there was 70.45% drug release within 48 hrs. Textural properties like adhesiveness, cohesiveness, hardness and gumminess and texture profile analysis (TPA) of zaltoprofen loaded lyotropic liquid crystalline gel could be evaluated with the help of cT3 texture analyzer. In vivo evaluation of this formulation was done by carrageenan induced rat paw edema anti-inflammatory model.
Penyuluhan dan Pelatihan Pembuatan Olahan Berbahan Pangan Lokal Kaya Zat Besi Guna Cegah Anemia Santriawati Pondok Pesantren Subulusalam Balikpapan
Authors: Gardiarini Praseptia , Dianovita Chardina , Gafur Abdul , Rustika Ranti
Published: October 2021

Santriwati yang ada di Subulusalam berusia sekitar 13-17 tahun yang merupakan kategori remaja putri. Remaja putri sangat rentan mengalami anemia, karena mengalami masa pubertas yang berupa menstruasi dan padatnya kegiatan serta aktivitas fisik yang mereka lakukan. Hal tersebut bila tidak ditunjang dengan nutrisi yang baik akan memungkinkan terjadinya anemia pada santriwati. Bayam, hati, dan tempe mrupakan bahan makanan yang memiliki kandungan zat besi, dan banyak digunakan dalam membuat makanan yang digunakan untuk meningkatkan sel darah merah. Tujuan pengabdian masyarakat ini adalah memberikan penyuluhan dan pelatihan untuk membuat bahan olahan yang mengandung zat besi. Produk yang dibuat adalah nuget hati bayam dan bronies tempe wortel. Metode yang digunakan adalah metode survey langsung pada menu yang dikonsumsi santriwati yang dilakukan ke pondok pesantren Subulus Salam. Hasil yang diperoleh adalah santriwati Subulus Salam mendapatkan pengetahuan yang lebih mengenai anemia dan cara untuk mencegahnya kemudian pengelola makanan santriwati Subulus Salam dapat membuat produk makanan yang kaya akan zat besi yaitu nugget hati bayam dan bronies tempe wortel yang memiliki cita rasa yang khas dan bergizi.
Peningkatan Hasil Belajar PAI Materi Shalat Kewajibanku Melalui Metode Demonstrasi Pada Siswa SDIT Al Islamiyah
Authors: Ulinuha Putra
Published: October 2021

Shalat merupakan ibadah yang terdiri dari perkataan maupun perbuatan yang dimulai dengan takbirotul ikhram dan diakhiri dengan salam. SDIT Al Islamiyah menggunakan metode demonstrasi yang digunakan dalam mata pelajaran PAI materi Shalat Kewajibanku kelas 3 semester 1.Tujuan penelitian adalah untuk mendapatkan gambaran implementasi  metode demonstrasi yang digunakan dalam mata pelajaran PAI materi Shalat Kewajibanku kelas 3 semester 1 untuk meningkatkan hasil belajar dan efektifitas metode demonstrasi yang digunakan dalam mata pelajaran PAI materi Shalat Kewajibanku kelas 3 semester 1 untuk meningkatkan hasil belajar . Penelitian ini dilakukan di SDIT Al Islamiyah dengan menggunakan pendekatan kualitatif. Pengumpulan data dilakukan melalui wawancara, observasi dan dokumentasi. Hasil penelitian ini pertama, gambaran impelemtasi metode demonstrasi yang digunakan dalam mata pelajaran PAI materi Shalat Kewajibanku kelas 3 semester 1 hasil belajarnya sangat baik dan memuaskan dengan guru PAI sebagai mediatornya dan praktek langsung di depan kelas. kedua, ffektifitas metode demonstrasi yang digunakan dalam mata pelajaran PAI materi Shalat Kewajibanku kelas 3 semester 1 hasil belajarnya sangat baik dan memuaskan. Karena guru PAI sudah merencakan dan mempersiapkan dengan baik. Semua peralatan yang digunakan untuk demonstrasi dalam pembelajaran sudah dicek dan maksimalkan agar membantu pembelajaran berjalan dengan baik.
Aplikasi Pengacak Soal Ujian Untuk Type Soal Berbasis Microsoft Word Menggunakan Metode Linear Congruent Method (LCM)
Authors: Limbong Tonni , Taufik Insan
Published: October 2021

Exam questions made by lecturers in general in an educational institution around 99% are made from Microsoft Word applications. This happens because of the ability or skill of the question maker and the facilities of the institution. The exam questions that have been made seem like a consumable model, even though the material from these questions still has a relationship with the subject. With this condition the existing questions are not necessary and do not have to be destroyed, it should be stored and made into a question bank. So on the next examination the test questions stored in the bank questions to be randomized again to make new questions as many as the number of questions needed so that the exam questions are presented far from static and color and each test for each participant will never be the same as previous questions. and also the implementation of semi-computerized exams do not need to require a computer laboratory.
This application is equipped with a randomization method, namely Linear Congruent Method (LCM), so that the questions that appear will never be the same each time printing a question in the form of executable (EXE), making it easier for study programs to make exam questions in multiple choices and in accordance with existing material in the syllabus and GBPP that apply from several lecturers who teach the same subject.
Reviewers’ Comments in Academic Journal Peer Review Reports: A Speech Act Theory Perspective
Authors: Tan Wee Chun
Published: October 2021

This study sought to investigate the linguistic functions of reviewers’ comments in academic journal peer review reports, primarily from a pragmatics perspective. Drawing on Searle’s (1976) Speech Act Theory (SAT), reviewers’ comments from 20 academic journal peer review reports were qualitatively analysed. The analysis revealed two main types of speech acts, directive and expressive speech acts, underlined the reviewers’ comments. Among the two types of speech acts, the directive speech act was preferred by the majority of the reviewers. It was also found that the expressive speech act was much more prominent when the reviewers provided negative comments. The results obtained suggest the need for a collegial peer review with more positive and constructive suggestions by reviewers.
Early Childhood Corner: Algebra in the Pre-K–2 Curriculum? Billy Goats and Bears Give Us the Answer
Authors: Elliott Portia C.
Published: October 2021

What should the algebra curriculum look like for preschool and primary-grade learners? I posed this lead-in question to a session in a mathematics methodology class for preservice early childhood and elementary teachers. Some of the teachers' answers indicated uncertainty. They gave vague, tentative answers about working with sequences and solving for unknowns. One participant's response resonated for others in the class: “I had a terrible time in high school algebra. I struggled to memorize the formulas for solving equations just as I had struggled to memorize my addition facts, multiplication tables, and long division in elementary school. What I remember of algebra, I would not wish on any child.” Other classmates murmured recognition of these feelings. Still another classmate added, “I got algebra. I even did well in trigonometry, but that doesn't mean that I understand algebra well enough to help children get it.”
Development of a Novel Processing Route for Dispersoid/Precipitation‐Strengthened High Conductive Copper Alloys by Using Metalized Nanoceramics in Additive Manufacturing
Authors: von Lintel Heinrich , Elsayed Abdelrahman , Mielewczyk Lukas , Eichmann Katja , Grothe Julia , Krupp Ulrich , Hariharan Avinash , Jahns Katrin
Published: December 2024

The growing efficiency demands in aerospace components, such as heat exchangers, require the production of more and more complex copper parts that offer both high strength and electrical conductivity. The CuCrZr alloy, widely used in this field, can be further enhanced by incorporating ceramic nanoparticles to increase strength with minimal impact on conductivity. Powders‐based additive manufacturing using laser (PBF‐LB/M), provides the flexibility to produce customized 3D components while enabling versatile alloy designs. A key challenge in manufacturing oxide‐dispersion‐strengthened copper alloys (Cu‐ODS) is the availability of appropriate powder feedstock. This study examines a process chain to produce dispersoid‐strengthened CuCr1Zr using in situ alloying with metalized nanoceramics. CuCr1Zr powder is created through gas atomization, while copper‐plated alumina (Cu‐Al2O3) nanoparticles are prepared using an organic surface activation method. Additive manufacturing is then conducted using green and red laser systems via PBF‐LB/M, followed by heat treatment at 480 °C for 2 h. The results show excellent densification and surface quality in printed samples, both with and without nanoparticle reinforcement. Additionally, it is found that lower levels of organic activation improve the relative density of the printed components, underscoring the need to optimize this process step for enhanced material properties.
Ligand Inter‐Relation Analysis Via Graph Theory Predicts Macrophage Response
Authors: Kang Nayeon , Hwang Jangsun , Jeong Daun , Choi Ji Hye , Thangam Ramar , Min Sunhong , Hong Hyunsik , Kim Dahee , Rha Hyunji , Lee Sungkyu , Jung Hwapyung , Kim Taeeon , Zare Iman , Jung Hee Joon , Najafabadi Alireza Hassani , Jung Hyun‐Do , Zhang Kunyu , Zhao Pengchao , Bian Liming , Kim Hong‐Kyu , Kim Jong Seung , Song Guosheng , Yoon Juyoung , Park Sung‐Gyu , Jang Woo Young , Kang Heemin
Published: December 2024

Graph theory has been widely used to quantitatively analyze complex networks of molecules, materials, and cells. Analyzing the dynamic complex structure of extracellular matrix can predict cell‐material interactions but has not yet been demonstrated. In this study, graph theory‐based mathematical modeling of RGD ligand graph inter‐relation is demonstrated by differentially cutting off RGD‐to‐RGD interlinkages with flexibly conjugated magnetic nanobars (MNBs) with tunable aspect ratio. The RGD‐to‐RGD interlinkages are less effectively cut off by MNBs with a lower aspect ratio, which decreases the shortest path while increasing the number of instances thereof, thereby augmenting RGD nano inter‐relation. This facilitates integrin recruitment of macrophages and thus actin fiber assembly and vinculin expression, which mediates pro‐regenerative polarization, involving myosin II, actin polymerization, and rho‐associated protein kinase. Unidirectional pre‐aligning or reversibly lifting highly elongated MNBs both increase RGD nano inter‐relation, which promotes host macrophage adhesion and switches their polarization from pro‐inflammatory to pro‐regenerative phenotype. The latter approach produces nano‐spaces through which macrophages can penetrate and establish RGD links thereunder. Using graph theory, this study presents the example of mathematically modeling the functionality of extracellular‐matrix‐mimetic materials, which can help elucidate complex dynamics of the interactions occurring between host cells and materials via versatile geometrical nano‐engineering.
Anti‐Fatigue Cellular Graphene Aerogel Through Multiscale Joint Strengthening
Authors: Tong Wenhao , Zhang Chengqi , Zhang Guoqiang , Pang Kai , Qin Huasong , Liu Yilun
Published: December 2024

Despite fatigue free of monolayer graphene, its assemblies, like cellular graphene aerogels (CGA), are usually suffering of frequent fatigue and inherent strength degradation in repeated loading. In this work, by employing multiscale modeling, the highly intrinsic anisotropic mechanical properties of the cell wall due to the layer‐by‐layer stacked graphene sheets are uncovered, which easily trigger the unique skeleton joints damage during repeated loading and contribute the primary fatigue mechanism of CGA. Conversely, multiscale joint strengthening strategies are proposed by interlayer crosslinking and joint curvation, improving the interlayer interaction, and decreasing interlayer stress during compression, respectively, so as to effectively suppress joint damage to improve fatigue performance of CGA. This work not only clarifies the underlying fatigue mechanism of 2D cellular materials but also highlights optimal design strategies for developing anti‐fatigue graphene cellular structures.
Angstrom‐Scale Defect‐Free Crystalline Membrane for Sieving Small Organic Molecules
Authors: Liu Guozhen , Chen Cailing , Mo Binyu , Zhou Guangyuan , Li Jiahui , Zhang Yaxin , Liu Gongping , Han Yu , Jin Wanqin
Published: December 2024

Crystalline membranes, represented by the metal‐organic framework (MOF) with well‐defined angstrom‐sized apertures, have shown great potential for molecular separation. Nevertheless, it remains a challenge to separate small molecules with very similar molecular size differences due to angstrom‐scale defects during membrane formation. Herein, a stepwise assembling strategy is reported for constructing MOF membranes with intrinsic angstrom‐sized lattice aperture lattice to separate organic azeotropic mixtures separation. The membrane is synthesized by redesigning the metal source, which reduces the coordination reaction rate to avoid cluster‐missing defects. Then, extra ligands are introduced to overcome the coordination steric hindrance to heal the linker‐missing defects. Ultralow‐dose transmission electron microscopy is used to realize a direct observation of the angstrom‐scale defects. For separating the challenging methanol‐containing ester or ether azeotropic mixtures with molecular size difference as small as <1 Å, the angstrom‐scale defect‐free MOF membrane exhibits an outstanding flux of ≈3700 g·m−2 h−1 and separation factor of ≈247–524, far beyond the upper‐bound of state‐of‐the‐arts membranes. This study offers a feasible strategy for precisely constructing angstrom‐confined spaces for diverse applications (e.g., separation, catalysis, and storage).
A Milk Extracellular Vesicle‐Based Nanoplatform Enhances Combination Therapy Against Multidrug‐Resistant Bacterial Infections
Authors: Qu Shaoqi , Yang Shuo , Xu Qingjun , Zhang Mengying , Gao Feng , Wu Yongning , Li Lin
Published: December 2024

The increasing occurrence of infections caused by multidrug‐resistant (MDR) bacteria drives the need for new antibacterial drugs. Due to the current lack of antibiotic discovery and development, new strategies to fight MDR bacteria are urgently needed. Efforts to develop new antibiotic adjuvants to increase the effectiveness of existing antibiotics and design delivery systems are essential to address this issue. Here, a bioinspired delivery system equipped with combination therapy and paracellular transport is shown to enhance the efficacy against bacterial infections by improving oral delivery. A screening platform is established using an in vitro‐induced high polymyxin‐resistant strain to acquire plumbagin, which enhances the efficacy of polymyxin. Functionalized milk extracellular vesicles (FMEVs) coloaded with polymyxin and plumbagin cleared 99% of the bacteria within 4 h. Mechanistic studies revealed that the drug combination damaged the membrane, disrupted energy metabolism, and accelerated bacterial death. Finally, FMEVs are efficiently transported transcellularly through the citric acid‐mediated reversible opening of the tight junctions and showed high efficacy against an MDR Escherichia coli‐associated peritonitis–sepsis model in mice. These findings provide a potential therapeutic strategy to improve the efficacy of combination therapy by enhancing oral delivery using a biomimetic delivery platform.
OTUD5 Protects Dopaminergic Neurons by Promoting the Degradation of α‐Synuclein in Parkinson's Disease Model
Authors: Song Xiaomeng , Liu Tengfei , Yu Lu , Ji Qiuran , Guo Xin , Zong Runzhe , Li Yiquan , Huang Gan , Xue Qidi , Fu Qingyi , Liu Bingyu , Zheng Yi , Chen Lin , Gao Chengjiang , Liu Huiqing
Published: December 2024

Defective clearance and accumulation of α‐synuclein (α‐Syn) is the key pathogenic factor in Parkinson's disease (PD). Recent studies emphasize the importance of E3 ligases in regulating the degradation of α‐Syn. However, the molecular mechanisms by which deubiquitinases regulate α‐Syn degradation are scarcely studied. In this study, it is found that the protein levels of α‐Syn are negatively regulated by ovarian tumor protease deubiquitinase 5 (OTUD5) which protects dopaminergic (DA) neurons in the PD model. Mechanistically, OTUD5 promotes K63‐linked polyubiquitination of α‐Syn independent of its deubiquitinating enzyme activity and mediates its endolysosomal degradation by recruiting the E3 ligase neural precursor cell expressed developmentally downregulated 4 (NEDD4). Furthermore, OTUD5 conditional knockout in DA neurons results in more severe α‐Syn related pathology and dyskinesia after injection of α‐Syn preformed fibrils (PFF). Overall, the data unveil a novel mechanism to regulate the degradation of α‐Syn and provide a new therapeutic strategy to alleviate DA neurodegeneration.
Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis‐Induced Acute Lung Injury
Authors: Lu Zongqing , Fang Pu , Li Shuai , Xia Dunling , Zhang Jingjing , Wu Xianghui , Pan Jingjing , Cai Haijian , Fu Lin , Sun Gengyun , You Qinghai
Published: December 2024

Circulating lactate is a critical biomarker for sepsis‐induced acute lung injury (S‐ALI) and is strongly associated with poor prognosis. However, whether elevated lactate directly promotes S‐ALI and the specific mechanism involved remain unclear. Here, this work shows that lactate causes pulmonary endothelial glycocalyx degradation and worsens ALI during sepsis. Mechanistically, lactate increases the lactylation of K18 of histone H3, which is enriched at the promoter of EGR1 and promotes its transcription, leading to upregulation of heparanase in pulmonary microvascular endothelial cells. In addition, multiple lactylation sites are identified in EGR1, and lactylation is confirmed to occur mainly at K364. K364 lactylation of EGR1 facilitates its interaction with importin‐α, in turn promoting its nuclear localization. Importantly, this work identifies KAT2B as a novel lactyltransferase whose GNAT domain directly mediates the lactylation of EGR1 during S‐ALI. In vivo, suppression of lactate production or genetic knockout of EGR1 mitigated glycocalyx degradation and ALI and improved survival outcomes in mice with polymicrobial sepsis. Therefore, this study reveals that the crosstalk between metabolic reprogramming in endothelial cells and epigenetic modifications plays a critical role in the pathological processes of S‐ALI.
Neurotransmitter‐Mimicking Nanovesicles Facilitate Postoperative Glioblastoma Stem Cell‐Specific Treatment for Preventing Tumor Recurrence
Authors: Liang Fuming , You Qing , Yu Bin , Wang Chen , Yang Yanlian , Zhu Ling , He Zhaohui
Published: December 2024

Survival quality of glioblastoma (GBM) patients remains undesirable despite the aggressive multimodal treatment methods implemented, which are strongly associated with tumor recurrence after surgical resection. Self‐renewal and strong tumourigenic capacity of glioblastoma stem cells (GSCs) at the narrow margin of the incision are essential factors driving tumor secondary strikes. Currently, the challenges in treating postoperative residual GSCs are mainly due to the lack of materials for incision and GSCs targeting. In this study, a neurotransmitter‐mimicking nanovesicle (PMVS‐P) based on platelet membrane‐derived vesicle (PMV) with anti‐GSC drug salinomycin (SAL)‐loading and polydopamine (PDA)‐surface is synthesized. PMVS‐P exhibits surgical incision targeting ability and specifically identified GSCs with highly expressed D2 dopamine receptor (D2DR), a central nervous system neurotransmitter receptor, thus suppressing GBM recurrence. This neurotransmitter‐mimicking nanovesicle primed GSC‐specific tumoricidal treatment with broadened applications for preventing tumor recurrence.
Functional Monomers Equipped Microgel System for Managing Parkinson's Disease by Intervening Chemokine Axis‐mediated Nerve Cell Communications
Authors: Jiang Lin , Zhang Xu , Wang Shun , Zhang Jiangkuan , Chen Junyang , Lu Jiachuan , Yao Liting , Jin Weiwei , Li Nan , Li Qing
Published: December 2024

The complex pathology of Parkinson's disease (PD) requires comprehensive understanding and multi‐pronged interventions for communication between nerve cells. Despite new developments in nanotechnology in the treatment of PD, in‐depth exploration of their biological effects, in particular, the specific mechanisms of inflammation inhibition are lacking. Herein, using the stable cascade catalysis channel formed by polydopamine (PDA), imidazole groups, and Cu ions, a microgel system comprising functional monomers [superoxide dismutase (SOD) with double bonds, PDA, 2‐methacryloyloxy ethyl phosphorylcholine (MPC), and Cu ions] is proposed for managing PD. The microgel can be efficiently delivered to the brain aided by MPC, after which a multi‐level regulatory strategy targeting neurons and microglia can be initiated. The catalytic activity cascade elicited by SOD and Cu ions can regulate the anti‐inflammatory phenotypic transformation of microglia by relieving oxidative stress. Meanwhile, the dopamine (DA) released from PDA can facilitate DA storage and neurogenesis, inhibiting CX3CL1 release and the CX3CR1 receptor on microglia and further regulating the CX3CL1/CX3CR1‐NF‐κB‐NLRP3 signaling pathway in microglia to inhibit neuroinflammation. Therefore, the proposed microgel delivery system with functional monomers represents a promising therapeutic strategy for managing neuroinflammation and promoting neurogenesis in PD by intervening chemokine axis‐mediated communication between neurons and microglia.
Propagation of Orientation Across Lengthscales in Sheared Self‐Assembling Hierarchical Suspensions via Rheo‐PLI‐SAXS
Authors: Ghanbari Reza , Terry Ann , Wojno Sylwia , Bek Marko , Sekar Kesavan , Sonker Amit Kumar , Nygård Kim , Ghai Viney , Bianco Simona , Liebi Marianne , Matic Aleksandar , Westman Gunnar , Nypelö Tiina , Kádár Roland
Published: December 2024

Simultaneous rheological, polarized light imaging, and small‐angle X‐ray scattering experiments (Rheo‐PLI‐SAXS) are developed, thereby providing unprecedented level of insight into the multiscale orientation of hierarchical systems in simple shear. Notably, it is observed that mesoscale alignment in the flow direction does not develop simultaneously across nano‐micro lengthscales in sheared suspensions of rod‐like chiral‐nematic (meso) phase forming cellulose nanocrystals. Rather, with increasing shear rate, orientation is observed first at mesoscale and then extends to the nanoscale, with influencing factors being the aggregation state of the hierarchy and concentration. In biphasic systems, where an isotropic phase co‐exists with self‐assembled liquid crystalline mesophase domains, the onset of mesodomain alignment towards the flow direction can occur at shear rates nearing one decade before a progressive increase in preferential orientation at nanoscale is detected. If physical confinement prevents the full formation of a cholesteric phase, mesoscale orientation occurs in shear rate ranges that correspond to de‐structuring at nanoscale. Interestingly, nano‐ and mesoscale orientations appear to converge only for biphasic suspensions with primary nanoparticles predominantly made up of individual crystallites and in a high‐aspect ratio nematic‐forming thin‐wall nanotube system. The nano‐micro orientation propagation is attributed to differences in the elongation and breakage of mesophase domains.
SPP1‐ITGα5/β1 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin‐Dependent PINK1/PARKIN Pathway Blockade
Authors: Gu Hanwen , Li Qi , Liu Zhenchuan , Li Yanlin , Liu Kaiwen , Kong Xiangzhen , Zhang Yuanqiang , Meng Qunbo , Song Kangle , Xie Qing , Gao Yuan , Cheng Lei
Published: December 2024

Low back pain (LBP) caused by nucleus pulposus degeneration and calcification leads to great economic and social burden worldwide. Unexpectedly, no previous studies have demonstrated the association and the underlying mechanism between nucleus pulposus tissue degeneration and calcification formation. Secreted Phosphoprotein 1 (SPP1) exerts crucial functions in bone matrix mineralization and calcium deposition. Here, a novel function of SPP1 is reported, namely that it can aggravate nucleus pulposus cells (NPs) degeneration by negatively regulating extracellular matrix homeostasis. The degenerated NPs have a higher mineralization potential, which is achieved by SPP1. Mechanistically, SPP1 can accelerate the degeneration of nucleus pulposus cells by activating integrin α5β1 (ITGα5/β1), aggravating mitochondrial damage and inhibiting mitophagy. SPP1‐ITGα5/β1 axis inhibits mitophagy by PINK1/PARKIN pathway blockade. In conclusion, SPP1 activates ITGα5/β1 to inhibit mitophagy, accelerates NPs degeneration, and induces calcification, thereby leading to intervertebral disc degeneration (IVDD) and calcification, identifying the potentially unknown mechanism and relationship between IVDD and calcification. Important insights are provided into the role of SPP1 in nucleus pulposus calcification in IVDD by inducing nucleus pulposus cell senescence through inhibition of mitophagy and may help develop potential new strategies for IVDD treatment.
Hybrid Cell Membrane‐Engineered Nanocarrier for Triple‐Action Strategy to Address Pseudomonas aeruginosa Infection
Authors: Zhang Shunhao , Chen Tianyu , Lu Weitong , Lin Yunfeng , Zhou Mi , Cai Xiaoxiao
Published: December 2024

Bacterial infections resistant to antimicrobial treatments, particularly those caused by Pseudomonas aeruginosa (P. aeruginosa), frequently lead to elevated mortality rates. Tackling this resistance using therapeutic combinations with varied mechanisms has shown considerable promise. In this study, a bioinspired nanocarrier is successfully designed and engineered for targeted antibiotic delivery and toxin/bacteria clearance. This is achieved by encapsulating antibiotic‐loaded framework nucleic acids with hybrid cell membranes acquired from neutrophils and platelets. By coating the hybrid membrane outside the shell, nanocarriers are endowed with the function of neutrophil‐like chemotaxis and platelet‐like bacteria adhesion to achieve the first stage of inflammation targeting. Based on the specific binding of bacteria toxin to the hybrid membrane, the release of antibiotic‐loaded framework nucleic acids is triggered by toxin‐mediated membrane lysis to fulfill the second stage of toxin neutralization and bacteria killing. Meanwhile, the immunomodulation potential of framework nucleic acids enables nanocarriers to accomplish the third stage of reversing the immunosuppressive microenvironment. In mouse models of acute and chronic P. aeruginosa pneumonia, the nanocarriers can reduce bacterial burden at a low dosage and decrease mortality with negligible toxicity. In sum, these findings have illustrated the remarkable capability of nanocarriers in treating recalcitrant bacterial infections.
Expanding Cas12a Activity Control with an RNA G‐Quadruplex at the 5′ end of CRISPR RNA
Authors: Huang Wenjuan , Wang Jiaqi , Wang Cheng , Liu Yuanfang , Li Wentao , Chen Qiaozhen , Zhai Junqiu , Xiang Zhenyang , Liu Chaoxing
Published: December 2024

Precise control of Cas12a activity is essential for the improvement of the detection limit of clinical diagnostics and the minimization of errors. This study addresses the challenge of controlling Cas12a activity, especially in the context of nucleic acid detection where the inherent incompatibility between isothermal amplification and CRISPR reactions complicates accurate diagnostics. An RNA G‐quadruplex (RG4) structure at the 5′ end of crRNA is introduced to modulate Cas12a activity accurately without the need for chemical modifications. The results indicate that the presence of RG4 does not significantly impact Cas12a's cleavage activity but can be controlled by RG4 stabilizers, enabling the suppression and subsequent restoration of Cas12a activity with potential for precise activity control. Moreover, the use of RG4 is expanded by incorporating it into split crRNA, introducing RG4 directly at the 5′ end of the direct repeat (DR) region, enabling tailored activity regulation for different targets by matching with various Spacer regions. Additionally, a light‐controlled one‐pot method for activating Cas12a is developed, thereby enhancing the accuracy and sensitivity of clinical samples. This study showcases the pioneering use of RG4 in manipulating Cas12a activity, streamlining diagnostics, and paving the way for advances in clinical nucleic acid testing.