bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a Switchable Filter for Reflectionless-Bandpass-to-Reflectionless-Bandstop Responses
Authors: Wu Gangxiong , Wu Hao , Qin Wei , Shi Jin , Zhang Wei , Lin Longlong , Li Qian
Published: February 2023

In this paper, a switchable filter based on the microstrip line (ML) with reflectionless-bandpass-to-reflectionless-bandstop responses is designed, theoretically validated, and fabricated. This single-port reflectionless bandpass filter (R-BPF) consists of a BPF and a shunt-connected bandstop section with terminated absorption resistors. The single-port reflectionless bandstop filter (R-BSF) is made of a BSF and a parallel bandpass circuit with terminated absorption resistors. These two reflectionless operational modes, namely R-BPF and R-BSF, are allowed to reconfigure the multifunctional filtering device using PIN diodes. In addition, a theoretical analysis of terminal impedance is performed to illustrate the working mechanism of the reflectionless response. To demonstrate the application of the proposed designs, a prototype of the switchable filter for R-BPF to R-BSF responses is fabricated and measured. For the R-BPF mode, the 3-dB fractional bandwidth (FBW) is 36.75% (1.67–2.42 GHz) with a 10-dB reflectionless bandwidth (RBW) of 1.36–2.58 GHz (i.e., FBW of 61.9%). For the R-BSF mode, the 10-dB bandwidth is 13% (1.85–2.11 GHz) with a 10.7-dB RBW of 1–3 GHz (i.e., FBW of 100%). An acceptable agreement between the measured and simulated results has been achieved.
Wideband Circularly Polarized Millimeter Wave Hemispherical Dielectric Resonator Antenna
Authors: Alanazi Meshari D. , Khamas Salam K.
Published: February 2023

A novel approach is proposed to design a circularly polarized (CP) hemispherical dielectric resonator antenna (DRA) with a wide axial ratio (AR) bandwidth by incorporating an additional dielectric substrate between the antenna and the ground plane. This is in addition to the lower feeding substrate that is located between the ground plane on one side and the feeding microstrip line on the other side. Adding another substrate on top of the ground plane provided an additional degree of freedom in the design that facilitated the achievement of ab 18% AR bandwidth. In addition, an integrated hemispherical DRA and perforated substrate configuration was utilized to achieve optimum effective substrate permittivity and overcome the DRA alignment and assembly challenges while maintaining the achieved wide CP bandwidth. A close agreement was achieved between measurements and simulations.
Design and Experiment of an Ultrasound-Assisted Corneal Trephination System
Authors: Xiao Jingjing , Chen Jialong , Li Mengqiong , Zhang Leiyu
Published: February 2023

According to the advantages of ultrasonic vibration cutting, an ultrasound-assisted corneal trepanation robotic system is developed to improve the accuracy of corneal trephination depth and corneal incision quality in corneal trephination operations. Firstly, we analyzed the reasons for the difficulty in controlling the depth of trephination in corneal transplantations from the perspective of the biomechanical properties of the cornea. Based on the advantages of ultrasonic vibration cutting, we introduced an ultrasonic-vibration-assisted cutting method for corneal trephination and analyzed the cutting mechanism. Secondly, we described the surgical demands of corneal trephination and listed the design requirements of a robotic system. Thirdly, we introduced the design details of said system, including the system’s overall structure, the ultrasound-assisted end effector, the key mechanisms of the robotic system, and the human–machine interaction interface. We designed the end effector based on ultrasonic vibration cutting and its eccentric adjustment system in an innovative way. Additionally, we then presented a procedure for robot-assisted corneal trephination. Finally, we performed several cutting experiments on grapes and porcine eyeballs in vitro. The results show that, compared with manual trephine, ultrasound-assisted corneal trephination has a better operation effect on the accuracy of corneal trephination depth and corneal incision quality.
An All-Silicon Resonant Pressure Microsensor Based on Eutectic Bonding
Authors: Chen Siyuan , Qin Jiaxin , Lu Yulan , Xie Bo , Wang Junbo , Chen Deyong , Chen Jian
Published: February 2023

In this paper, an all-Si resonant pressure microsensor based on eutectic bonding was developed, which can eliminate thermal expansion coefficient mismatches and residual thermal stresses during the bonding process. More specifically, the resonant pressure microsensor included an SOI wafer with a pressure-sensitive film embedded with resonators, which was eutectically bonded with a silicon cap for vacuum encapsulation. The all-Si resonant pressure microsensor was carefully designed and simulated numerically, where the use of the silicon cap was shown to effectively address temperature disturbances of the microsensor. The microsensor was then fabricated based on MEMS processes where eutectic bonding was adopted to link the SOI wafer and the silicon cap. The characterization results showed that the temperature disturbances of the resonant pressure microsensor encapsulated with the silicon cap were quantified as −0.82 Hz/°C of the central resonator and −2.36 Hz/°C of the side resonator within a temperature range from −40 °C to 80 °C, which were at least eight times lower than that of the microsensor encapsulated with the glass cap. Compared with the microsensor using the glass cap, the all-silicon microsensor demonstrated an accuracy improvement from 0.03% FS to 0.01% FS and a reduction in short-term frequency fluctuations from 3.2 Hz to 1.5 Hz.
Mastering DNA Content Estimation by Flow Cytometry as an Efficient Tool for Plant Breeding and Biodiversity Research
Authors: Fomicheva Maria , Domblides Elena
Published: February 2023

Flow cytometry gives a unique opportunity to analyze thousands of individual cells for multiple parameters in a course of minutes. The most commonly used flow cytometry application in plant biology is estimation of nuclear DNA content. This becomes an indispensable tool in different areas of plant research, including breeding, taxonomy, plant development, evolutionary biology, populational studies and others. DNA content analysis can provide an insight into natural ploidy changes that reflect evolutionary processes, such as interspecific hybridization and polyploidization. It is also widely used for processing samples with biotechnologically induced ploidy changes, for instance, plants produced by doubled haploid technology. Absolute genome size data produced by cytometric analysis serve as useful taxon-specific markers since genome size vary between different taxa. It often allows the distinguishing of species within a genus or even different subspecies. Introducing flow cytometry method in the lab is extremely appealing, but new users face a significant challenge of learning instrument management, quality sample preparation and data processing. Not only is flow cytometry a complex method, but plant samples have unique features that make plants a demanding research subject. Without proper training, researchers risk damaging the expensive instrument or publishing poor quality data, artifacts or unreproducible results. We bring together information from our experience, key papers and online resources to provide step by step protocols and give a starting point for exploring the abundant cytometry literature.
Soil Carbon and Nitrogen Forms and Their Relationship with Nitrogen Availability Affected by Cover Crop Species and Nitrogen Fertilizer Doses
Authors: Braos Lucas Boscov , Carlos Roberta Souto , Bettiol Aline Carla Trombeta , Bergamasco Marina Ali Mere , Terçariol Maira Caroline , Ferreira Manoel Evaristo , da Cruz Mara Cristina Pessôa
Published: February 2023

Cover crops and N fertilization strongly impact the forms of soil organic C and N and their availability, which change the responses of plants to N fertilization and soil organic C accumulation. Our study objectives were to evaluate the effects of cover crops and N doses on soil total and soluble C and N contents, N fractions, and potentially available N in a long-term no-till experiment. The experiment was conducted in a randomized block design with split plots and four replicates. The main treatments were cover crops species, jack bean, lablab bean, millet, velvet bean, and fallow cultivated prior to maize. Secondary treatments included two doses of mineral N (0 and 120 kg ha−1). Soil samples were collected at depths of 0–5, 5–10, 10–20, and 20–40 cm, which were analyzed for total and water-soluble C and N contents, N fractions (acid hydrolysis method), and potentially available N (hot KCl solution and direct steam distillation methods). Cover crop velvet bean resulted in the highest soil organic carbon levels, and cover crop millet plus fertilization resulted in the highest levels of soil total N. The amino sugar was the largest N fraction, which decreased by 8% with N fertilization. The soluble C and N content strongly correlated with total and available N content. The changes in soil N were influenced by cover crop species and fertilization and the interactions of both, so the combination of fertilization regime and cover crops must be chosen with care. Additionally, legumes are a good source of plant and soil N in systems with low input of N via fertilizer; however, the combination of N fertilizer with legumes can reduce soil N reserves, leading to its long-term depletion.
Changes in Blood Markers of Oxidative Stress, Inflammation and Cardiometabolic Patients with COPD after Eccentric and Concentric Cycling Training
Authors: Valero-Breton Mayalen , Valladares-Ide Denisse , Álvarez Cristian , Peñailillo Reyna S. , Peñailillo Luis
Published: February 2023

Chronic obstructive pulmonary disease (COPD) patients manifest muscle dysfunction and impaired muscle oxidative capacity, which result in reduced exercise capacity and poor health status. This study examined the effects of 12-week eccentric (ECC) and concentric (CONC) cycling training on plasma markers of cardiometabolic health, oxidative stress, and inflammation in COPD patients. A randomized trial in which moderate COPD was allocated to ECC (n = 10; 68.2 ± 10.0 year) or CONC (n = 10; 71.1 ± 10.3 year) training groups. Participants performed 12-week ECC or CONC training, 2–3 sessions per week, 10 to 30 min per session. Before and after training, peak oxygen consumption, maximal power output (VO2peak and POmax), and time-to-exhaustion (TTE) tests were performed. Plasma antioxidant and oxidative markers, insulin resistance, lipid profile, and systemic inflammation markers were measured before and after training at rest. VO2peak, POmax and TTE remained unchanged after ECC and CONC. CONC induced an increase in antioxidants (p = 0.01), while ECC decreased antioxidant (p = 0.02) markers measured at rest. CONC induced lesser increase in oxidative stress following TTE (p = 0.04), and a decrease in insulin resistance (p = 0.0006) compared to baseline. These results suggest that CONC training induced an increase in insulin sensitivity, antioxidant capacity at rest, and lesser exercise-induced oxidative stress in patients with moderate COPD.
Dietary Intervention on Overweight and Obesity after Confinement by COVID-19
Authors: Ramírez-Manent José Ignacio , Tomás-Gil Pilar , Martí-Lliteras Pau , Coll Villalonga Josep Lluis , Martínez-Almoyna Rifá Emilio , López-González Ángel Arturo
Published: February 2023

Background: Obesity has become a public health problem in our society and is associated with many diseases, including type 2 diabetes mellitus, cardiovascular diseases, dyslipidemia, respiratory diseases, and cancer. Several studies relate weight loss in obese patients to improved anthropometric measurements and cardiometabolic risk. The objective of our study was to evaluate anthropometric changes, analytical parameters, insulin resistance, fatty liver, and metabolic scales, after a personalized weight loss program, through dietary advice to increase adherence to the Mediterranean diet and a motivational booster via mobile SMS messaging. Methods: Intervention study on a sample of 1964 workers, in which different anthropometric parameters were evaluated before and after dietary intervention: the metabolic score of insulin resistance; non-alcoholic fatty liver disease using different scales; metabolic syndrome; atherogenic dyslipidemia; and the cardiometabolic index. A descriptive analysis of the categorical variables was performed, by calculating the frequency and distribution of the responses for each one. For quantitative variables, the mean and standard deviation were calculated, since they followed a normal distribution. Bivariate association analysis was performed by applying the chi-squared test (corrected by Fisher’s exact statistic when conditions required it) and Student’s t-test for independent samples (for comparison of means). Results: The population subjected to the Mediterranean diet improved in all the variables evaluated at 12 months of follow-up and compliance with the diet. Conclusions: Dietary advice on a Mediterranean diet and its reinforcement with reminder messages through the use of mobile phones may be useful to improve the parameters evaluated in this study and reduce the cardiometabolic risk of patients.
The Effectiveness of Wearable Devices in Non-Communicable Diseases to Manage Physical Activity and Nutrition: Where We Are?
Authors: Natalucci Valentina , Marmondi Federica , Biraghi Michele , Bonato Matteo
Published: February 2023

Wearable devices are increasingly popular in clinical and non-clinical populations as a tool for exercise prescription, monitoring of daily physical activity and nutrition, and health-related parameters management. In this regard, smart devices not only assist people in pursuing a healthier lifestyle, but also provide a constant stream of physiological and metabolic data for management of non-communicable diseases (NCDs). Although the benefits of lifestyle-based interventions (exercise and nutrition) for NCDs are well known, the potential of wearable devices to promote healthy behaviors in clinical populations is still controversial. In this narrative review, we aimed to discuss the current application of wearable devices in NCDs, highlighting their role in prescribing and monitoring daily physical activity and dietary habits in the population living with chronic diseases. None of the studies considered specifically addressed the efficacy of the use of wearable devices, and limited are those that incorporate monitoring of both physical activity and nutrition for NCDs. However, there is evidence that such devices have helped improve physical activity levels, physical fitness, body composition, and metabolic and psychological parameters. Therefore, the authors believe that the benefits obtained from the use of wearable devices are likely to translate to public health and represent one of the important tools for the development of prevention plans in everyday life and clinical practice for optimal patient management.
Evaluation of the Association between Amount and Type of Milk Consumption and Periodontitis: Data from the Korea National Health and Nutrition Examination Survey (2016–2018)
Authors: Min Eun Jeong , Jeong Siseong , Park Jun-Beom
Published: February 2023

This study evaluated the association between the consumption of milk and having severe periodontitis. It is based on the information from the 2016–2018 Korea National Health and Nutrition Examination Survey. Severe periodontitis was characterized as a community periodontal index of code 4. A total of 18,034 individual respondents (7835 men and 10,199 women) without missing values were included in this study. Adjusted odds ratios and a 95% confidence interval of periodontitis in a multivariate logistic regression model for the amount of milk consumption were 0.774 [0.633–0.945] after the adjustment of confounding factors. This trend was maintained in a subgroup analysis of males with adjusted odds ratios, with a 95% confidence interval of 0.705 [0.538–0.924]. Overall, the findings showed a negative association between Korean adults’ milk consumption and the prevalence of severe periodontitis. Men with higher milk consumption were more likely to have a lower prevalence of severe periodontitis regardless of age, body mass index, smoking or drinking habits, education, income, region, and physical exercise, diabetes mellitus, hypertension, metabolic syndrome, white blood cell count and toothbrushing frequency. By contrast, in women, the amount of milk consumption was not significantly associated with severe periodontitis. The amount of milk consumed was discovered to be a potential risk indicator for severe periodontitis in men in this study.
Does Aging Have an Impact on Vitamin C Status and Requirements? A Scoping Review of Comparative Studies of Aging and Institutionalisation
Authors: Carr Anitra C. , Zawari Masuma
Published: February 2023

The global healthcare burden of an aging population continues to increase, with nearly a quarter of the total global burden of disease attributable to people aged ≥60 years. Older people are at greater risk of micronutrient deficiencies, including immune-supportive vitamin C, which is both a contributor to and a consequence of acute and chronic illnesses. However, whether healthy aging, per se, is associated with depleted vitamin C status and increased requirements for the vitamin is less certain. A systematic scoping review was carried out to assess comparative studies that reported the vitamin C status and prevalence of deficiency in older versus younger people and in older people relative to residential status. Furthermore, vitamin C requirements were assessed through comparative studies reporting vitamin C status and pharmacokinetics in older people relative to younger people. Overall, there was limited evidence to suggest that healthy aging, per se, is related to lower vitamin C status or higher requirements for the vitamin. However, institutionalised elderly had lower vitamin C status and enhanced vitamin C requirements, primarily as a result of low intakes and/or chronic illnesses, which were not being met by hospital or residential diets. Because institutionalised elderly are vulnerable to malnutrition and micronutrient deficiencies, it is imperative that appropriate nutritional interventions are instigated to provide optimal micronutrient intake to support healthy aging.
Mediation of 10-Year Cardiovascular Disease Risk between Inflammatory Diet and Handgrip Strength: Base on NHANES 2011–2014
Authors: Xie Zechun , Wang Ling , Sun Mengzi , Wang Rui , Li Jing , Wang Xuhan , Guo Ruirui , Dong Yibo , Wang Yuxiang , Li Bo
Published: February 2023

Objective: Dietary inflammatory index (DII) and handgrip strength (HGS) were correlated, and both were associated with cardiovascular disease (CVD). However, the role of the 10-year CVD risk in the relationship between DII and grip strength remains uncertain. Methods: This study involved 5691 adults from the National Health and Nutrition Examination Survey (NHANES) in 2011–2014. Dietary inflammation, 10-year CVD risk and relative grip strength were assessed by the Dietary Inflammation Index, the Framingham Risk Score (FRS) and handgrip strength adjusted BMI. Linear regression analyses and mediation analysis were used to explore these associations. Results: Both DII and 10-year CVD risk were negatively associated with relative handgrip strength, and DII was positively associated with 10-year CVD risk. Additionally, 10-year CVD risk partially mediated the association between DII and relative handgrip strength by a 11.8% proportion. Specifically, the mediating effect of the 10-year risk of CVD varied by gender and age. Conclusions: Reducing the 10-year risk of CVD attenuates the effect of an inflammatory diet on relative grip strength impairment. Therefore, we recommend reducing the effect of inflammatory diet on grip strength impairment by controlling any of the FRS parameters, such as lowering blood pressure and smoking cessation, especially with targeted measures for different populations.
Beneficial Effects of ε-Viniferin on Obesity and Related Health Alterations
Authors: Gómez-Zorita Saioa , Milton-Laskibar Iñaki , Eseberri Itziar , Beaumont Pauline , Courtois Arnaud , Krisa Stéphanie , Portillo María P.
Published: February 2023

Viniferin is a phenolic compound belonging to the group of stilbenoids. In particular, ε-viniferin is a dimer of resveratrol, found in many plant genders, among which grapes (Vitis vinifera) are a primary source. Due to the fact that ε-viniferin is mainly present in the woody parts of plants, their use as a source of this bioactive compound is a very interesting issue in a circular economy. Both, in vitro studies carried out in pre-adipocytes and mature adipocytes and in vivo studies addressed in mice show that ε-viniferin is able to reduce fat accumulation. Moreover, it prevents the development of some obesity co-morbidities, such as type 2 diabetes, dyslipidemias, hypertension and fatty liver. ε-viniferin can be absorbed orally, but it shows a very low bioavailability. In this scenario, further research on animal models is needed to confirm the effects reported in a great number of studies; to determine which metabolites are involved, including the main one responsible for the biological effects observed and the mechanisms that justify these effects. In a further phase, human studies should be addressed in order to use ε-viniferin as a new tool for obesity management, as a nutraceutical or to be included in functional foods.
Hindmilk as a Rescue Therapy in Very Preterm Infants with Suboptimal Growth Velocity
Authors: Alshaikh Belal N. , Festival Jannette , Reyes Loredo Adriana , Yusuf Kamran , Towage Zainab , Fenton Tanis R. , Wood Christel
Published: February 2023

Despite advances in neonatal nutrition, very preterm infants remain at increased risk of extrauterine growth faltering. This prospective study aimed to examine the effect of hindmilk, the milk at the end of a breast expression session, on growth and plasma fatty acids (FAs) of infants born <30 weeks’ gestation who had been on full enteral feeds for ≥2 weeks and had a weight gain of <15 g/kg/day despite optimizing energy and protein intakes. Weight and plasma FAs were assessed before and two weeks after feeding hindmilk. Growth anthropometrics were assessed weekly for four weeks. Paired t-tests and multiple linear regression were used for statistical analyses of data from 34 infants and their 29 mothers. There was a significant increase in weight gain in the two weeks after feeding hindmilk (MD 3.9, 95%CI 1.2–6.5 g/kg/day). Weight Z-scores were larger at two weeks (MD 0.61, 95%CI 0.02–1.20) and onwards. Head circumference Z-scores were larger at three weeks (MD 0.83, 95%CI 0.20–1.47) and onwards. Plasma linoleic acid (LA) and α-linolenic acid (ALA) increased after feeding hindmilk. In conclusion, hindmilk may improve weight and head growth and increase LA and ALA in very preterm infants with suboptimal growth. A large randomized controlled trial is required to examine and validate the potential benefits of hindmilk.
Impact of Vitamin B12 Insufficiency on the Incidence of Sarcopenia in Korean Community-Dwelling Older Adults: A Two-Year Longitudinal Study
Authors: Choi Seongmin , Chon Jinmann , Lee Seung Ah , Yoo Myung Chul , Chung Sung Joon , Shim Ga Yang , Soh Yunsoo , Won Chang Won
Published: February 2023

The longitudinal effect of B12 insufficiency on sarcopenia has not yet been investigated in older adults. We aimed to study the impact of B12 levels on alterations in muscle mass, function and strength over two years. Non-sarcopenic older adults (n = 926) aged 70–84 were included. Using the Korean Frailty and Aging Cohort Study, this two-year longitudinal study used data across South Korea. The tools used for assessing muscle criteria were based on the Asian Working Group for Sarcopenia guidelines. Participants were divided into the insufficiency (initial serum B12 concentration < 350 pg/mL) and sufficiency groups (≥350 pg/mL). Logistic regression analyses were performed to evaluate the effect of initial B12 concentration on sarcopenia parameters over a two-year period. In women, multivariate analysis showed that the B12 insufficiency group had a significantly higher incidence of low SPPB scores (odds ratio [OR] = 3.28, 95% confidence interval [CI] = 1.59–6.76) and sarcopenia (OR = 3.72, 95% CI = 1.10–12.62). However, the B12 insufficiency group did not have a greater incidence of sarcopenia or other parameters in men. Our findings suggest B12 insufficiency negatively impacts physical performance and increases the incidence of sarcopenia only in women.
Wanted Dead or Alive: Skeletal Structure Alteration of Cold-Water Coral Desmophyllum pertusum (Lophelia pertusa) from Anthropogenic Stressors
Authors: Krueger Erica Terese , Büscher Janina V. , Hoey David A. , Taylor David , O’Reilly Peter J. , Crowley Quentin G.
Published: February 2023

Ocean acidification (OA) has provoked changes in the carbonate saturation state that may alter the formation and structural biomineralisation of calcium carbonate exoskeletons for marine organisms. Biomineral production in organisms such as cold-water corals (CWC) rely on available carbonate in the water column and the ability of the organism to sequester ions from seawater or nutrients for the formation and growth of a skeletal structure. As an important habitat structuring species, it is essential to examine the impact that anthropogenic stressors (i.e., OA and rising seawater temperatures) have on living corals and the structural properties of dead coral skeletons; these are important contributors to the entire reef structure and the stability of CWC mounds. In this study, dead coral skeletons in seawater were exposed to various levels of pCO2 and different temperatures over a 12-month period. Nanoindentation was subsequently conducted to assess the structural properties of coral samples’ elasticity (E) and hardness (H), whereas the amount of dissolution was assessed through scanning electron microscopy. Overall, CWC samples exposed to elevated pCO2 and temperature show changes in properties which leave them more susceptible to breakage and may in turn negatively impact the formation and stability of CWC mound development.
Safety and Efficacy of Buprenorphine-Naloxone in Pregnancy: A Systematic Review of the Literature
Authors: Ordean Alice , Tubman-Broeren Meara
Published: February 2023

The prevalence of opioid use among pregnant people has been increasing over the past few decades, with a parallel increase in the rate of neonatal abstinence syndrome. Opioid agonist treatment (OAT) including methadone and buprenorphine is the recommended management method for opioid use disorders during pregnancy. Methadone has been extensively studied during pregnancy; however, buprenorphine was introduced in the early 2000s with limited data on the use of different preparations during pregnancy. Buprenorphine-naloxone has been incorporated into routine practice; however, only a few studies have investigated the use of this medication during pregnancy. To determine the safety and efficacy of this medication, we conducted a systematic review of maternal and neonatal outcomes among buprenorphine-naloxone-exposed pregnancies. The primary outcomes of interest were birth parameters, congenital anomalies, and severity of neonatal abstinence syndrome. Secondary maternal outcomes included the OAT dose and substance use at delivery. Seven studies met the inclusion criteria. Buprenorphine-naloxone doses ranged between 8 and 20 mg, and there was an associated reduction of opioid use during pregnancy. There were no significant differences in gestational age at delivery, birth parameters, or prevalence of congenital anomalies between buprenorphine-naloxone-exposed neonates and those exposed to methadone, buprenorphine monotherapy, illicit opioids, or no opioids. In studies comparing buprenorphine-naloxone to methadone, there were reduced rates of neonatal abstinence syndrome requiring pharmacotherapy. These studies demonstrate that buprenorphine-naloxone is a safe and effective opioid agonist treatment for pregnant people with OUD. Further large-scale, prospective data collection is required to confirm these findings. Patients and clinicians may be reassured about the use of buprenorphine-naloxone during pregnancy.
Nornidulin, A New Inhibitor of Plasmodium falciparum Malate: Quinone Oxidoreductase (PfMQO) from Indonesian Aspergillus sp. BioMCC f.T.8501
Authors: Cahyono Alfian Wika , Fitri Loeki Enggar , Winarsih Sri , Prabandari Erwahyuni Endang , Waluyo Danang , Pramisandi Amila , Chrisnayanti Evita , Dewi Diana , Siska Eka , Nurlaila Nurlaila , Nugroho Nuki Bambang , Nozaki Tomoyoshi , Suciati Suciati
Published: February 2023

This study aimed to obtain a microbial active compound as a novel antimalarial drug from Indonesian isolates. Target-based assays were used to screen for antimalarial activity against the parasite mitochondrial, Plasmodium falciparum malate:quinone oxidoreductase (PfMQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against PfMQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by Aspergillus sp. BioMCC f.T.8501 demonstrated stable PfMQO inhibitory activity. Several purification stages, including OCC, TLC, and HPLC, were performed to obtain bioactive compounds from this active extract. All purification steps were followed by an assay against PfMQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited PfMQO activity at IC50 of 51 µM and P. falciparum 3D7 proliferation in vitro at IC50 of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian Aspergillus sp. BioMCC f.T.8501 as a novel inhibitor of PfMQO, which showed inhibitory activity against the proliferation of P. falciparum 3D7 in vitro.
Phytofabrication and Characterisation of Zinc Oxide Nanoparticles Using Pure Curcumin
Authors: Alallam Batoul , Doolaanea Abd Almonem , Alfatama Mulham , Lim Vuanghao
Published: February 2023

Zinc oxide and curcumin, on their own and in combination, have the potential as alternatives to conventional anticancer drugs. In this work, zinc oxide nanoparticles (ZnO NPs) were prepared by an eco-friendly method using pure curcumin, and their physicochemical properties were characterised. ATR-FTIR spectra confirmed the role of curcumin in synthesising zinc oxide curcumin nanoparticles (Green-ZnO-NPs). These nanoparticles exhibited a hexagonal wurtzite structure with a size and zeta potential of 27.61 ± 5.18 nm and −16.90 ± 0.26 mV, respectively. Green-ZnO-NPs showed good activity towards studied bacterial strains, including Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. The minimum inhibitory concentration of Green-ZnO-NPs was consistently larger than that of chemically synthesised ZnO NPs (Std-ZnO-NPs) or mere curcumin, advocating an additive effect between the zinc oxide and curcumin. Green-ZnO-NPs demonstrated an efficient inhibitory effect towards MCF-7 cells with IC50 (20.53 ± 5.12 μg/mL) that was significantly lower compared to that of Std-ZnO-NPs (27.08 ± 0.91 μg/mL) after 48 h of treatment. When Green-ZnO-NPs were tested against Artemia larvae, a minimised cytotoxic effect was observed, with LC50 being almost three times lower compared to that of Std-ZnO-NPs (11.96 ± 1.89 μg/mL and 34.60 ± 9.45 μg/mL, respectively). This demonstrates that Green-ZnO-NPs can be a potent, additively enhanced combination delivery/therapeutic agent with the potential for anticancer therapy.
Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future
Authors: Ramírez-Jiménez Fernando , Pavón-Romero Gandhi Fernando , Velásquez-Rodríguez Juancarlos Manuel , López-Garza Mariana Itzel , Lazarini-Ruiz José Fernando , Gutiérrez-Quiroz Katia Vanessa , Teran Luis M.
Published: February 2023

The discovery of the mechanism underlying allergic disease, mouse models of asthma, and bronchoscopy studies provided initial insights into the role of Th2-type cytokines, including interlukin (IL)-4, IL-5 and IL-13, which became the target of monoclonal antibody therapy. Omalizumab, Benralizumab, Mepolizumab, Reslizumab, and Tezepelumab have been approved. These biologicals have been shown to be good alternative therapies to corticosteroids, particularly in severe asthma management, where they can improve the quality of life of many patients. Given the success in asthma, these drugs have been used in other diseases with type 2 inflammation, including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and chronic urticaria. Like the Th2-type cytokines, chemokines have also been the target of novel monoclonal therapies. However, they have not proved successful to date. In this review, targeted therapy is addressed from its inception to future applications in allergic diseases.
The Regioselective Conjugation of the 15-nt Thrombin Aptamer with an Optimized Tripeptide Sequence Greatly Increases the Anticoagulant Activity of the Aptamer
Authors: Varizhuk Irina V. , Tsvetkov Vladimir B. , Toropygin Ilya Yu. , Stomakhin Andrey A. , Kolganova Natalia A. , Surzhikov Sergei A. , Timofeev Edward N.
Published: February 2023

Currently, oligonucleotide therapy has emerged as a new paradigm in the treatment of human diseases. In many cases, however, therapeutic oligonucleotides cannot be used directly without modification. Chemical modification or the conjugation of therapeutic oligonucleotides is required to increase their stability or specificity, improve their affinity or inhibitory characteristics, and address delivery issues. Recently, we proposed a conjugation strategy for a 15-nt G-quadruplex thrombin aptamer aimed at extending the recognition interface of the aptamer. In particular, we have prepared a series of designer peptide conjugates of the thrombin aptamer, showing improved anticoagulant activity. Herein, we report a new series of aptamer–peptide conjugates with optimized peptide sequences. The anti-thrombotic activity of aptamer conjugates was notably improved. The lead conjugate, TBA–GLE, was able to inhibit thrombin-induced coagulation approximately six-fold more efficiently than the unmodified aptamer. In terms of its anticoagulant activity, the TBA–GLE conjugate approaches NU172, one of the most potent G-quadruplex thrombin aptamers. Molecular dynamics studies have confirmed that the principles applied to the design of the peptide side chain are efficient instruments for improving aptamer characteristics for the proposed TBA conjugate model.
Chitosan Surface-Modified PLGA Nanoparticles Loaded with Cranberry Powder Extract as a Potential Oral Delivery Platform for Targeting Colon Cancer Cells
Authors: Mostafa Mona M. , Amin Maha M. , Zakaria Mohamed Y. , Hussein Mohammed Abdalla , Shamaa Marium M. , Abd El-Halim Shady M.
Published: February 2023

Nutraceutical cranberry powder extract (CBPE) has distinct polyphenols inhibiting colon cancer growth and proliferation. However, its oral therapeutic efficacy is hindered because of its low permeability. This study aims to formulate chitosan surface-modified PLGA nanoparticles (CS-PLGA NPs) for encapsulating CBPE and modulating its release rate, permeation, cell targeting, and, therefore, its cytotoxicity. A full 23 factorial design is employed to scrutinize the effect of lactide/glycolide ratio, PLGA weight, and stabilizer concentrations on entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formula (F4) shows spherical particles with a relatively high EE% (72.30 ± 2.86%), an appropriate size of 370.10 ± 10.31 nm, PDI; 0.398 ± 0.001, and ZP; −5.40 ± 0.21 mV. Alongside the ATR-FTIR outcomes, the chitosan surface-modified formula (CS-F4) demonstrates a significant increase in particle size (417.67 ± 6.77 nm) and a shift from negative to positive zeta potential (+21.63 ± 2.46 mV), confirming the efficiency of surface modification with chitosan. The intestinal permeability of F4 and CS-F4 is significantly increased by 2.19- and 3.10-fold, respectively, compared to the CBPE solution, with the permeability coefficient (Papp) being 2.05 × 10−4 cm/min and 2.91 × 10−4 cm/min, for F4 and CS-F4, respectively, compared to the CBPE solution, 9.36 × 10−5 cm/min. Moreover, CS-F4 evidences significant caspase-3 protein level expression stimulation and significant inhibition of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription-3 (STAT-3) protein expression levels, confirming the superiority of CS-F4 for targeting HT-29 cells. Briefly, CS-PLGA NPs could be regarded as a prosperous delivery system of CBPE with enhanced permeation, cell targeting, and antitumor efficacy.
Experimental Methods for the Biological Evaluation of Nanoparticle-Based Drug Delivery Risks
Authors: Pandey Ramendra Pati , Vidic Jasmina , Mukherjee Riya , Chang Chung-Ming
Published: February 2023

Many novel medical therapies use nanoparticle-based drug delivery systems, including nanomaterials through drug delivery systems, diagnostics, or physiologically active medicinal products. The approval of nanoparticles with advanced therapeutic and diagnostic potentials for applications in medication and immunization depends strongly on their synthesizing procedure, efficiency of functionalization, and biological safety and biocompatibility. Nanoparticle biodistribution, absorption, bioavailability, passage across biological barriers, and biodistribution are frequently assessed using bespoke and biological models. These methods largely rely on in vitro cell-based evaluations that cannot predict the complexity involved in preclinical and clinical studies. Therefore, assessing the nanoparticle risk has to involve pharmacokinetics, organ toxicity, and drug interactions manifested at multiple cellular levels. At the same time, there is a need for novel approaches to examine nanoparticle safety risks due to increased constraints on animal exploitation and the demand for high-throughput testing. We focus here on biological evaluation methodologies that provide access to nanoparticle interactions with the organism (positive or negative via toxicity). This work aimed to provide a perception regarding the risks associated with the utilization of nanoparticle-based formulations with a particular focus on assays applied to assess the cytotoxicity of nanomaterials.
PLGA Particles in Immunotherapy
Authors: Horvath Dennis , Basler Michael
Published: February 2023

Poly(lactic-co-glycolic acid) (PLGA) particles are a widely used and extensively studied drug delivery system. The favorable properties of PLGA such as good bioavailability, controlled release, and an excellent safety profile due to the biodegradable polymer backbone qualified PLGA particles for approval by the authorities for the application as a drug delivery platform in humas. In recent years, immunotherapy has been established as a potent treatment option for a variety of diseases. However, immunomodulating drugs rely on targeted delivery to specific immune cell subsets and are often rapidly eliminated from the system. Loading of PLGA particles with drugs for immunotherapy can protect the therapeutic compounds from premature degradation, direct the drug delivery to specific tissues or cells, and ensure sustained and controlled drug release. These properties present PLGA particles as an ideal platform for immunotherapy. Here, we review recent advances of particulate PLGA delivery systems in the application for immunotherapy in the fields of allergy, autoimmunity, infectious diseases, and cancer.
Nanobiotechnology-Enabled mRNA Stabilization
Authors: Xian He , Zhang Yue , Yu Chengzhong , Wang Yue
Published: February 2023

mRNA technology has attracted enormous interest due to its great therapeutic potential. Strategies that can stabilize fragile mRNA molecules are crucial for their widespread applications. There are numerous reviews on mRNA delivery, but few focus on the underlying causes of mRNA instability and how to tackle the instability issues. Herein, the recent progress in nanobiotechnology-enabled strategies for stabilizing mRNA and better delivery is reviewed. First, factors that destabilize mRNA are introduced. Second, nanobiotechnology-enabled strategies to stabilize mRNA molecules are reviewed, including molecular and nanotechnology approaches. The impact of formulation processing on mRNA stability and shelf-life, including freezing and lyophilization, are also briefly discussed. Lastly, our perspectives on challenges and future directions are presented. This review may provide useful guidelines for understanding the structure–function relationship and the rational design of nanobiotechnology for mRNA stability enhancement and mRNA technology development.
mRNA-Based Therapeutics in Cancer Treatment
Authors: Sun Han , Zhang Yu , Wang Ge , Yang Wen , Xu Yingjie
Published: February 2023

Over the past two decades, significant technological innovations have led to messenger RNA (mRNA) becoming a promising option for developing prophylactic and therapeutic vaccines, protein replacement therapies, and genome engineering. The success of the two COVID-19 mRNA vaccines has sparked new enthusiasm for other medical applications, particularly in cancer treatment. In vitro-transcribed (IVT) mRNAs are structurally designed to resemble naturally occurring mature mRNA. Delivery of IVT mRNA via delivery platforms such as lipid nanoparticles allows host cells to produce many copies of encoded proteins, which can serve as antigens to stimulate immune responses or as additional beneficial proteins for supplements. mRNA-based cancer therapeutics include mRNA cancer vaccines, mRNA encoding cytokines, chimeric antigen receptors, tumor suppressors, and other combination therapies. To better understand the current development and research status of mRNA therapies for cancer treatment, this review focused on the molecular design, delivery systems, and clinical indications of mRNA therapies in cancer.
Study on the Acousto-Optic Coupling Effect of a One-Dimensional Hetero-Optomechanical Crystal Nanobeam Resonator
Authors: Lan Jianxu , Wen Xiaodong , Sun Xiaowei , Liu Xixuan , Wang Yiwen , Han Genliang
Published: February 2023

The optomechanical crystal nanobeam resonator has attracted the attention of researchers due to its high optomechanical coupling rate and small modal volume. In this study, we propose a high-optomechanical-coupling-rate heterostructure with a gradient cavity, and the optomechanical rates of the single mirror and hetero-optomechanical crystal nanobeam resonators are calculated. The results demonstrate that the heterostructure based on the utilization of two mirror regions realizes better confinement of the optical and mechanical modes. In addition, the mechanical breathing mode at 9.75 GHz and optical mode with a working wavelength of 1.17 μm are demonstrated with an optomechanical coupling rate g0 = 3.81 MHz between them, and the mechanical quality factor is increased to 3.18 × 106.
Topology Optimization of Low-Loss Z-Bend 2D Photonic Crystal Waveguide
Authors: Liu Gang , Wang Fei , Gao Yongpan , Jia Baonan , Guan Xiaoning , Lu Pengfei , Song Haizhi
Published: February 2023

In this article, we design a low-loss, high-bandwidth Z-bend photonic silicon crystal waveguide bending in a triangular lattice through topology optimization. Based on the topological optimization method, we change the relative position of air holes in the global scope to maximize the transmittance and bandwidth of the waveguide. The simulation results indicate that the transmission characteristics can be effectively improved with our method. After the optimization, the loss of the waveguide can be reduced to −5 dB and the bandwidth can increase to 160 nm. Our research has great significance for further optimizing the propagation of light in photonic crystals.
Highly Branched Tannin-Tris(2-aminoethyl)amine-Urea Wood Adhesives
Authors: Zhang Bengang , Chen Xinyi , Pizzi Antonio , Petrissans Mathieu , Dumarcay Stephane , Petrissans Anelie , Zhou Xiaojian , Du Guanben , Colin Baptiste , Xi Xuedong
Published: February 2023

Condensed tannin copolymerized with hyperbranched tris(2-aminoethyl)amine-urea formed by amine-amido deamination yields a particleboard thermosetting adhesive without any aldehydes satisfying the requirements of relevant standards for the particleboard internal bond strength. The tannin–triamine–urea cures well at 180 °C, a relatively low temperature for today’s particleboard hot pressing. As aldehydes were not used, the formaldehyde emission was found to be zero, not even in traces due to the heating of wood. The effect is ascribed to the presence of many reactive sites, such as amide, amino, and phenolic groups belonging to the three reagents used. The tannin appears to function as an additional cross-linking agent, almost a nucleating agent, for the triamine–urea hyperbranched oligomers. Chemical analysis by MALDI ToF and 13C NMR has shown that the predominant cross-linking reaction is that of the substitution of the tannin phenolic hydroxyls by the amino groups of the triamine. The reaction of tannin with the still-free amide groups of urea is rather rare, but it may occur with the rarer tannin flavonoid units in which the heterocyclic ring is opened. Due to the temperature gradient between the surfaces and the board core in the particleboard during hot pressing, the type and the relative balance of covalent and ionic bonds in the resin structure may differ in the surfaces and the board core.
Sisal-Fiber-Reinforced Polypropylene Flame-Retardant Composites: Preparation and Properties
Authors: Wang Zhenhua , Feng Weili , Ban Jiachen , Yang Zheng , Fang Xiaomin , Ding Tao , Liu Baoying , Zhao Junwei
Published: February 2023

Natural-fiber-reinforced polypropylene (PP) composites with a series of advantages including light weight, chemical durability, renewable resources, low in cost, etc., are being widely used in many fields such as the automotive industry, packaging, and construction. However, the flammability of plant fiber and the PP matrix restricts the application range, security, and use of these composites. Therefore, it is of great significance to study the flame retardants of such composites. In this paper, sisal-fiber-reinforced polypropylene (PP/SF) flame-retardant composites were prepared using the two-step melt blending method. The flame retardant used was an intumescent flame retardant (IFR) composed of silane-coated ammonium polyphosphate (Si-APP) and pentaerythritol (PER). The influence of different blending processes on the flammability and mechanical properties of the composites was analyzed. The findings suggested that PP/SF flame-retardant composites prepared via different blending processes showed different flame-retardant properties. The (PP/SF)/IFR composite prepared by PP/SF secondary blending with IFR showed excellent flame-retardant performance, with a limited oxygen index of about 28.3% and passing the UL-94 V-0 rating (3.2 mm) in the vertical combustion test. Compared with the (PP/IFR) /SF composite prepared by a matrix primarily blended with IFR and then secondly blended with SF, the peak heat release rate (pk HRR) and total heat release (THR) of the (PP/SF)/IFR composite decreased by 11.3% and 13.7%, respectively. In contrast, the tensile strength of the (PP/SF)/IFR system was 5.3% lower than that of the (PP/IFR)/SF system; however, the overall mechanical (tensile, flexural, and notched impact) properties of the composites prepared using three different mixing processes were similar.