bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility Study of Anaerobic Baffled Reactor Coupled with Anaerobic Filter Followed by Membrane Filtration for Wastewater Treatment
Authors: Khan Aamir , Khan Sher Jamal , Miran Waheed , Zaman Waqas Qamar , Aslam Alia , Shahzad Hafiz Muhammad Aamir
Published: January 2023

The performance of a Decentralized Wastewater Treatment System (DWTS) comprising an Anaerobic Baffled Reactor (ABR) and an Anaerobic Filter (AF) and Membrane Filtration (MF) module was studied for domestic wastewater treatment. The efficiency of the system was evaluated by running ABR at four different HRTs (14, 12, 10, and 8 h) resulting in COD removal efficiencies of 74, 72, 69, and 65%, respectively. The performance of AF using four different filtration media, i.e., PVC pipe (25 mm), PVC pipe (20 mm), PVC pipe (15 mm), and Kaldnes K3, was determined at optimized HRT (12 h). Among all the filtration media tested, the highest performance efficiency of the system was found with the PVC pipe (20 mm), which showed COD, TP, and TKN removal of 79, 32, and 63%, respectively. The efficacy of the system was proven via significant COD and turbidity removal of 94.6 and 87.2%, respectively, by the combined system.
An Investigation of the Mechanical, Thermal and Electrical Properties of an AA7075 Alloy Reinforced with Hybrid Ceramic Nanoparticles Using Friction Stir Processing
Authors: Khoshaim Ahmed B. , Moustafa Essam B. , Alazwari Mashhour A. , Taha Mohammed A.
Published: January 2023

Aluminum AA7075, graphene nanoplates (GNP), boron nitride (BN), and vanadium carbide (VC) are used to fabricate hybrid nanocomposite matrices. BN and VC serve as secondary reinforcement particles in the fabrication of hybrid composites, with graphene (GNP) as a key component of the hybrid process. Friction stir processing (FSP) was used to manufacture the composite matrix; it also has a major role in improving the microstructure’s grain refinement, as well as the reinforcing of the particles, which play a crucial role in limiting grain growth during the dynamic recrystallization process. Consequently, the grain sizes of the nanocomposite AA7075/GNPs, hybrid composites AA7075/GNPs+BN, and hybrid composites AA7075/GNPs+BN+VC were decreased by an average of 10.3 times compared to the base alloy. The SEM analysis demonstrated that the dispersion of the hybrid reinforcement particles was performed, and the particles were dispersed uniformly throughout the metal matrix. The mechanical characteristics of the hybrid AA7075/GNPs+BN+VC include the highest compression stress and hardness values due to the homogeneity of the hybridization process between the BN and VC particles. The GNPs reduce the electrical conductivity by 7.3% less than the base alloy. In comparison, when hybridized with BN and VC, it is reduced by 24.4% and 31.1%, respectively. In addition, the inclusion of thermally insulating materials, such as BN and VC, decreases the thermal conductivity of the hybrid composite metal matrices.
Multi-Objective Optimization of Fiber Laser Cutting of Stainless-Steel Plates Using Taguchi-Based Grey Relational Analysis
Authors: Turkkan Yusuf Alptekin , Aslan Muhammed , Tarkan Alper , Aslan Özgür , Yuce Celalettin , Yavuz Nurettin
Published: January 2023

Stainless-steel has become a widely preferred material type in the marine, aerospace, sanitary, industrial equipment, and construction industries due to its superior corrosion resistance, high mechanic properties, high strength, formability, and thermal and electrical conductivity. In this study, a multi-objective optimization method based on grey relational analysis was employed to optimize the fiber laser-cutting parameters of cutting speed, focal position, frequency, and duty cycle. Surface roughness and kerf width, which are the two most important parameters that determine laser-cutting quality, were simultaneously optimized. In order to assign the optimum level of each parameter individually, the Taguchi technique was applied. The cutting surface morphology was examined according to the grey relational grade with a 3D optical profilometer, and maps of the cutting surfaces were created. According to the results achieved using Analysis of Variance (ANOVA), it was seen that the parameters that affected surface roughness and kerf width the most were duty cycle, with a contribution rate of 49.01%, and frequency, with a contribution rate of 31.2%. Frequency was the most important parameter in terms of multiple responses, with a contribution rate of 18.55%. Duty cycle and focal position were the second and third most effective parameters, respectively. It was determined that the optimum parameter values for minimum surface roughness and minimum kerf width that could be obtained with the fiber laser cutting of 20 mm thick AISI 304L (DIN EN 1.4301) material were 310 mm/min cutting speed, −11 mm focal position, 105 Hz frequency, and 60% duty cycle.
Characterization of Vapor Capillary Geometry in Laser Beam Welding of Copper with 515 nm and 1030 nm Laser Beam Sources by Means of In Situ Synchrotron X-ray Imaging
Authors: Kaufmann Florian , Forster Carola , Hummel Marc , Olowinsky Alexander , Beckmann Felix , Moosmann Julian , Roth Stephan , Schmidt Michael
Published: January 2023

Laser welding of copper is being used with increasing demand for contacting applications in electric components such as batteries, power electronics, and electric drives. With its local, non-contact energy input and high automation capability enabling reproducible weld quality, this joining technology represents a key enabler of future mobility systems. However, a major challenge in process design is the combination of energy efficiency and precise process guidance in terms of weld seam depth and defect prevention (i.e., spatter and melt ejections) due to the high electrical and thermal conductivity of copper. High-power lasers in the near infrared wavelength range (𝜆 ≈ 1 μm) and excellent beam quality provide an established joining solution for this purpose; nevertheless, the low absorptivity (≤5%) advocates novel beam sources at visible wavelengths due to altered absorptivity (40% at 515 nm) characteristics as an improved tool. In order to understand the influence of laser wavelength and process parameters on the vapor capillary geometry, in situ synchrotron investigations on Cu-ETP with 515 nm and 1030 nm laser sources with the same spot diameter are compared. The material phase contrast analysis was successfully used to distinguish keyhole and melt pool phase boundaries during the welding process. A significantly different sensitivity of the keyhole depth in relation to the feed rate was found, which is increased for the infrared laser. This behavior could be attributed to the increased effect of multiple reflections at 1030 nm.
PPAR Signaling Maintains Metabolic Homeostasis under Hypothermia in Freshwater Drum (Aplodinotus grunniens)
Authors: Wu Ningyuan , Wen Haibo , Xu Pao , Chen Jianxiang , Xue Miaomiao , Li Jianlin , Wang Meiyao , Song Changyou , Li Hongxia
Published: January 2023

Aplodinotus grunniens, known as freshwater drum, is a kind of eurythermal freshwater fish that is widely distributed in North America. In 2019, our research group reached a milestone on its artificial breeding and cultivation and have investigated its physiological adaption to the environment, providing a breakthrough and prospects for aquaculture. However, its adaptability and metabolic homeostasis to hypothermia is not fully understood. In this experiment, cold stress was conducted at 18 °C (LT18) and 10 °C (LT10) with 25 °C as control (Con) for 8 days to explore the effects of short-term hypothermia on the physiology and metabolism of freshwater drum. From the results, the level of free essential amino acids in LT18 and LT10 decreased significantly after 2 days cold stress compared with Con. Furthermore, plasma total triglyceride (TG) content and lipase (LPS) activity were decreased at LT10 for 2d. With RNA-seq in the liver, metabolic-related signaling, especially amino acid synthesis and lipid metabolism, was inhibited by hypothermia. Specifically, the PPAR signaling pathway is correlated with the inhibition of lipid and amino acid metabolism induced by hypothermia. These data confirmed that PPAR signaling maintains lipid and amino acid metabolic homeostasis during cold stress. These results give a theoretical foundation for hypothermia resistance in the area of metabolic homeostasis for freshwater drum.
Appraising the Effects of Metabolic Traits on the Risk of Glaucoma: A Mendelian Randomization Study
Authors: Wang Kai , Yang Fangkun , Liu Xin , Lin Xueqi , Yin Houfa , Tang Qiaomei , Jiang Li , Yao Ke
Published: January 2023

Metabolic traits are associated with the risk of developing glaucoma in observational studies. To assess whether theses associations reflect causality, we conducted a Mendelian randomization (MR) study. Our study included up to 20,906 glaucoma cases and 438,188 controls. Genetic instruments associated with the concerned 11 exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. Summary-level data for glaucoma were obtained from the UK Biobank, the GERA study, and the FinnGen consortium. Univariable and multivariable MR analyses were conducted separately in two populations. Our results showed that higher genetic liability to type 2 diabetes (T2D) was causally and independently associated with an increased risk of glaucoma (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06–1.16; p = 4.4 × 10−6). The association for T2D persisted after multivariable adjustment. In addition, higher genetically predicted systolic blood pressure (SBP), fasting glucose (FG), and HbA1c, were also suggestively associated with glaucoma risk. The OR was 1.08 (95% CI, 1.01–1.16; p = 0.035) for SBP, 1.24 (95% CI, 1.05–1.47; p = 0.011) for FG, and 1.28 (95% CI, 1.01–1.61; p = 0.039) for HbA1c. No evidence was observed to support the causal effects of body mass index and blood lipids for glaucoma. This study suggests a causal role for diabetes, as well as possible roles for higher SBP, FG, and HbA1c in the development of glaucoma. Further validation is needed to assess the potential of these risk factors as pharmacological targets for glaucoma prevention.
Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices
Authors: Rodrigues Oliveira Sonia M. , Rebocho António , Ahmadpour Ehsan , Nissapatorn Veeranoot , de Lourdes Pereira Maria
Published: January 2023

Type 1 diabetes mellitus (T1DM) is the most common autoimmune chronic disease in young patients. It is caused by the destruction of pancreatic endocrine β-cells that produce insulin in specific areas of the pancreas, known as islets of Langerhans. As a result, the body becomes insulin deficient and hyperglycemic. Complications associated with diabetes are life-threatening and the current standard of care for T1DM consists still of insulin injections. Lifesaving, exogenous insulin replacement is a chronic and costly burden of care for diabetic patients. Alternative therapeutic options have been the focus in these fields. Advances in molecular biology technologies and in microfabrication have enabled promising new therapeutic options. For example, islet transplantation has emerged as an effective treatment to restore the normal regulation of blood glucose in patients with T1DM. However, this technique has been hampered by obstacles, such as limited islet availability, extensive islet apoptosis, and poor islet vascular engraftment. Many of these unsolved issues need to be addressed before a potential cure for T1DM can be a possibility. New technologies like organ-on-a-chip platforms (OoC), multiplexed assessment tools and emergent stem cell approaches promise to enhance therapeutic outcomes. This review will introduce the disorder of type 1 diabetes mellitus, an overview of advances and challenges in the areas of microfluidic devices, monitoring tools, and prominent use of stem cells, and how they can be linked together to create a viable model for the T1DM treatment. Microfluidic devices like OoC platforms can establish a crucial platform for pathophysiological and pharmacological studies as they recreate the pancreatic environment. Stem cell use opens the possibility to hypothetically generate a limitless number of functional pancreatic cells. Additionally, the integration of stem cells into OoC models may allow personalized or patient-specific therapies.
Performance Testing of Micro-Electromechanical Acceleration Sensors for Pavement Vibration Monitoring
Authors: Ye Zhoujing , Wei Ya , Yang Biyu , Wang Linbing
Published: January 2023

Pavement vibration monitoring under vehicle loads can be used to acquire traffic information and assess the health of pavement structures, which contributes to smart road construction. However, the effectiveness of monitoring is closely related to sensor performance. In order to select the suitable acceleration sensor for pavement vibration monitoring, a printed circuit board (PCB) with three MEMS (micro-electromechanical) accelerometer chips (VS1002, MS9001, and ADXL355) is developed in this paper, and the circuit design and software development of the PCB are completed. The experimental design and comparative testing of the sensing performance of the three MEMS accelerometer chips, in terms of sensitivity, linearity, noise, resolution, frequency response, and temperature drift, were conducted. The results show that the dynamic and static calibration methods of the sensitivity test had similar results. The influence of gravitational acceleration should be considered when selecting the range of the accelerometer to avoid the phenomenon of over-range. The VS1002 has the highest sensitivity and resolution under 3.3 V standard voltage supply, as well as the best overall performance. The ADXL355 is virtually temperature-independent in the temperature range from −20 °C to 60 °C, while the voltage reference values output by the VS1002 and MS9001 vary linearly with temperature. This research contributes to the development of acceleration sensors with high precision and long life for pavement vibration monitoring.
High Frequency MEMS Capacitive Mirror for Space Applications
Authors: Bagolini Alvise , Sitar Anze , Porcelli Luca , Boscardin Maurizio , Dell’Agnello Simone , Delle Monache Giovanni
Published: January 2023

Free space optics laser communication using modulating retroreflectors (MR) is a challenging application for an active mirror, due to the high frequencies (>100 kHz) required to enable sufficient data transfer. Micro Electromechanical (MEMS) mirrors are a promising option for high-frequency applications, given the very small moving mass typical of such devices. Capacitive MEMS mirrors are presented here for free space communications, based on a novel fabrication sequence that introduces a single-layer thin film aluminum mirror structure with an underlying silicon oxide sacrificial layer. The use of aluminum instead of gold as a mirror layer diminishes the heating generated by the absorption of the sun’s radiation once the mirrors exit the earth’s atmosphere. Thanks to the novel fabrication sequence, the presented mirror devices have a full range actuation voltage of less than 40 V, and a high operational frequency with an eigenfrequency above 2 MHz. The devices were manufactured and characterized, and their main parameters were obtained from experimental data combined with finite element analysis, thus enabling future design optimization of the reported MEMS technology. By optical characterization of the far field diffraction pattern, good mirror performance was demonstrated.
Trapping of a Single Microparticle Using AC Dielectrophoresis Forces in a Microfluidic Chip
Authors: Wang Yanjuan , Tong Ning , Li Fengqi , Zhao Kai , Wang Deguang , Niu Yijie , Xu Fengqiang , Cheng Jiale , Wang Junsheng
Published: January 2023

Precise trap and manipulation of individual cells is a prerequisite for single-cell analysis, which has a wide range of applications in biology, chemistry, medicine, and materials. Herein, a microfluidic trapping system with a 3D electrode based on AC dielectrophoresis (DEP) technology is proposed, which can achieve the precise trapping and release of specific microparticles. The 3D electrode consists of four rectangular stereoscopic electrodes with an acute angle near the trapping chamber. It is made of Ag–PDMS material, and is the same height as the channel, which ensures the uniform DEP force will be received in the whole channel space, ensuring a better trapping effect can be achieved. The numerical simulation was conducted in terms of electrode height, angle, and channel width. Based on the simulation results, an optimal chip structure was obtained. Then, the polystyrene particles with different diameters were used as the samples to verify the effectiveness of the designed trapping system. The findings of this research will contribute to the application of cell trapping and manipulation, as well as single-cell analysis.
Filtenna with Frequency Reconfigurable Operation for Cognitive Radio and Wireless Applications
Authors: Abdelghany Mahmoud A. , Ali Wael A. E. , Mohamed Hesham A. , Ibrahim Ahmed A.
Published: January 2023

A reconfigurable wideband monopole antenna is introduced in this paper for cognitive radio and wireless applications. The reconfigurability was achieved by four varactor diodes embedded in the band pass filter (BPF) structure which was integrated with the suggested antenna through its feed line. The simulated impedance characteristics coped with the measured ones after fabricating the suggested model with/without the reconfigurable BPF. Furthermore, the model achieved the desired radiation characteristics in terms of radiation pattern with acceptable gain values at the selected frequencies within the achieved frequency range (1.3–3 GHz).
A Simulation Optimization Factor of Si(111)-Based AlGaN/GaN Epitaxy for High Frequency and Low-Voltage-Control High Electron Mobility Transistor Application
Authors: Guan He , Shen Guiyu , Liu Shibin , Jiang Chengyu , Wu Jingbo
Published: January 2023

The effects of barrier layer thickness, Al component of barrier layer, and passivation layer thickness of high-resistance Si (111)-based AlGaN/GaN heterojunction epitaxy on the knee-point voltage (Vknee), saturation current density (Id-sat), and cut-off frequency (ft) of its high electron mobility transistor (HEMT) are simulated and analyzed. A novel optimization factor OPTIM is proposed by considering the various performance parameters of the device to reduce the Vknee and improve the Id-sat on the premise of ensuring the ft. Based on this factor, the optimized AlGaN/GaN epitaxial structure was designed with a barrier layer thickness of 20 nm, an Al component in the barrier layer of 25%, and a SiN passivation layer of 6 nm. By simulation, when the gate voltage Vg is 0 V, the designed device with a gate length of 0.15 μm, gate-source spacing of 0.5 μm, and gate-drain spacing of 1 μm presents a high Id-sat of 750 mA/mm and a low Vknee of 2.0 V and presents ft and maximum frequency (fmax) as high as 110 GHz and 220 GHz, respectively. The designed device was fabricated and tested to verify the simulation results. We demonstrated the optimization factor OPTIM can provide an effective design method for follow-up high-frequency and low-voltage applications of GaN devices.
Tunable MEMS-Based Terahertz Metamaterial for Pressure Sensing Application
Authors: Lai Wei-Hsi , Li Binghui , Fu Shih-Huai , Lin Yu-Sheng
Published: January 2023

In this study, a tunable terahertz (THz) metamaterial using the micro-electro-mechanical system (MEMS) technique is proposed to demonstrate pressure sensing application. This MEMS-based tunable metamaterial (MTM) structure is composed of gold (Au) split-ring resonators (SRRs) on patterned silicon (Si) substrate with through Si via (TSV). SRR is designed as a cantilever on the TSV structure. When the airflow passes through the TSV from bottom to up and then bends the SRR cantilever, the SRR cantilever will bend upward. The electromagnetic responses of MTM show the tunability and polarization-dependent characteristics by bending the SRR cantilever. The resonances can both be blue-shifted from 0.721 THz to 0.796 THz with a tuning range of 0.075 THz in transverse magnetic (TM) mode and from 0.805 THz to 0.945 THz with a tuning range of 0.140 THz in transverse electric (TE) mode by changing the angle of SRR cantilever from 10° to 45°. These results provide the potential applications and possibilities of MTM design for use in pressure and flow rate sensors.
Impacts of Small-Scale Effect and Nonlinear Damping on the Nonlinear Vibrations of Electrostatic Microresonators
Authors: Meng Dayao , Huang Kun , Xu Wei
Published: January 2023

Although the small-scale effect and nonlinear damping on the nonlinear vibration of microbeam electrostatic resonators are important, they have been overlooked by researchers. We use the slender beam model including the small-scale effect and nonlinear damping to investigate the nonlinear vibrations of the electrostatic resonators in the present paper. We apply the Galerkin method on a nonlinear partial differential equation to obtain the nonlinear ordinary differential equations for the first and third modes. The two equations include constant terms. The multiple-scale method is used to obtain the approximate analytical solutions of the two equations. The approximate analytical solutions discover the effects of driving electric field, small-scale effect, and nonlinear damping on structural vibrations. The results suggest that the small-scale effect, the direct current (DC) voltage, and the alternating current (AC) voltage have some critical effects on the vibrations of microresonators.
Mining Wastes as Road Construction Material: A Review
Authors: Segui Pauline , Safhi Amine el Mahdi , Amrani Mustapha , Benzaazoua Mostafa
Published: January 2023

The mining industry manages large volumes of tailings, sludge, and residues that represent a huge environmental issue. This fact has prompted research into valorization of these wastes as alternative aggregates for concrete production, embankments, pavement material, etc. The use of mining wastes as a resource for construction presents two benefits: conserving natural resources and reducing the environmental impacts of mining. In the case of road construction, the use of mining wastes has not yet been developed on a large scale and there is a major lack of specific legislation. This gap is due to the variety of exploited rocks, the diversity of tailings, mine residues, or valuable by-products slated for valorization, and the environmental specifics. This paper presents a review on recycling mine wastes as road construction material, including waste rock and mine tailings. Those materials were mostly used in infrastructure where soils had initially poor geotechnical properties (low bearing capacity, frost susceptibility, swelling risk, etc.). Different mining wastes were used directly or stabilized by a hydraulic binder through geopolymerization or, in some cases, with bituminous treatment. Overall, the use of mine wastes for road construction will have a considerable environmental impact by reducing the volume of waste and offering sustainable raw materials.
Recent Strategies for High-Performing Indoor Perovskite Photovoltaics
Authors: Mularso Kelvian T. , Jeong Ji-Young , Han Gill Sang , Jung Hyun Suk
Published: January 2023

The development of digital technology has made our lives more advanced as a society familiar with the Internet of Things (IoT). Solar cells are among the most promising candidates for power supply in IoT sensors. Perovskite photovoltaics (PPVs), which have already attained 25% and 40% power conversion efficiencies for outdoor and indoor light, respectively, are the best candidates for self-powered IoT system integration. In this review, we discuss recent research progress on PPVs under indoor light conditions, with a focus on device engineering to achieve high-performance indoor PPVs (Id-PPVs), including bandgap optimization and defect management. Finally, we discuss the challenges of Id-PPVs development and its interpretation as a potential research direction in the field.
An Assessment of the Oral and Inhalation Acute Toxicity of Nickel Oxide Nanoparticles in Rats
Authors: Lyons-Darden Tara , Blum Jason L. , Schooley Mark W. , Ellis Melissa , Durando Jennifer , Merrill Daniel , Oller Adriana R.
Published: January 2023

Nickel oxide nanoparticles (NiO NPs) have been the focus of many toxicity studies. However, acute toxicity studies that identify toxicological dose descriptors, such as an LC50 or LD50, are lacking. In this paper, the acute toxicity of NiO NPs was evaluated in albino-derived Sprague-Dawley rats through OECD guideline studies conducted by both the oral and inhalation routes of exposure. The animals were assessed for mortality, body weight, behavioral observations, and gross necropsy. Results from previously conducted (unpublished) acute inhalation studies with larger NiO microparticles (MPs) are also included for comparison. Mortality, the primary endpoint in acute toxicity studies, was not observed for rats exposed to NiO NPs via either the oral or inhalation exposure routes, with a determined LD50 of >5000 mg/kg and an LC50 > 5.42 mg/L, respectively. Our results suggest that these NiO NPs do not exhibit serious acute toxicity in rats or warrant an acute toxicity classification under the current GHS classification criteria. This aligns with similar results for NiO MPs from this and previously published studies.
Radio Frequency Identification Temperature/CO2 Sensor Using Carbon Nanotubes
Authors: Habib Ayesha , Akram Safia , Ali Mohamed R. , Muhammad Taseer , Zainab Sajeela , Jehangir Shafia
Published: January 2023

In the world of digitization, different objects cooperate with the Internet of Things (IoT); these objects also amplify using sensing and data processing structures. Radio frequency identification (RFID) has been identified as a key enabler technology for IoT. RFID technology has been used in different conventional applications for security, goods storage, transportation and asset management. In this paper, a fully inkjet-printed chipless radio frequency identification (RFID) sensor tag is presented for the wireless identification of tagged objects. The dual polarized tag consists of two resonating structures functioning wirelessly. One resonator works for encoding purpose and other resonator is used as a CO2/temperature sensor. The sensing behavior of the tag relies on the integration of a meandered structure comprising of multi-wall carbon nanotubes (MWCNT). The MWCNT is highly sensitive to CO2 gas. The backscattered response of the square-shaped cascaded split ring resonators (SRR) is analyzed through a radar cross-section (RCS) curve. The overall tag dimension is 42.1 mm × 19.5 mm. The sensing performance of the tag is examined and optimized for two different flexible substrates, i.e., PET and Kapton®HN. The flexible tag structure has the capability to transmit 5-bit data in the frequency bands of 2.36–3.9 GHz and 2.37–3.89 GHz, for PET and Kapton®HN, respectively. The proposed chipless RFID sensor tag does not require any microchip or a power source, so it has a great potential for low-cost and automated temperature/CO2 sensing applications.
Exposure to the Dutch Famine in Early Gestation and Cognitive Function and Decline in Older Age
Authors: Wiegersma Aline Marileen , Boots Amber , Roseboom Tessa J. , de Rooij Susanne R.
Published: January 2023

People exposed to the 1944–1945 Dutch famine in early gestation performed worse on a selective attention task at age 58 and reported more cognitive problems at age 72. We here hypothesized that undernutrition in early gestation is associated with poorer cognitive functioning in older age and a higher rate of cognitive decline. We tested this hypothesis in the Dutch famine birth cohort in men and women combined and separately. We assessed cognitive function using a Stroop-like, trail-making and 15-word task (at ages 68 and 74) and the Montreal cognitive assessment as well as self-perceived cognitive problems (at age 74) in 73 men (n = 34) and women (n = 39). We compared cognitive function and decline (change in cognitive function between age 68 and 74) between those exposed in early gestation and those not exposed (born before or conceived after the famine). Although in both men and women cognitive function declined from age 68 to 74, cognitive task scores and the rate of decline did not differ between those exposed or unexposed to famine. At age 74, men exposed to famine in early gestation more often reported cognitive problems, although this was not statistically different from unexposed men (OR 3.1 [95%CI 0.7 to 13.0]). We did not find evidence of increased cognitive decline after prenatal undernutrition. Selective participation and mortality may have hampered our ability to detect potential true effects. The self-perceived cognitive problems among men who had been exposed to famine in early gestation might be an indication of future dementia risk.
Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits
Authors: Park Sunmin , Liu Meiling , Huang Shaokai
Published: January 2023

Genetic and environmental factors are associated with developing and progressing duodenal ulcer (DU) risk. However, the exact nature of the disease pathophysiology and the single nucleotide polymorphism (SNP)—lifestyle interaction has yet to be determined. The purpose of the present study was to examine the SNPs linked to DU risk and their interaction with lifestyles and diets in a large hospital-based cohort of Asians. Based on an earlier diagnosis, the participants were divided into the DU (case; n = 1088) and non-DU (control, n = 56,713) groups. The SNP associated with DU risk were obtained from a genome-wide association study (GWAS), and those promoted genetic impact with SNP–SNP interactions were identified with generalized multifactor dimensionality reduction analysis. The interaction between polygenic risk score (PRS) calculated from the selected genetic variants and nutrient were examined. They were related to actin modification, immune response, and cell migration by modulating leucine-rich repeats (LRR) domain binding, Shaffer interferon regulatory factor 4 (IRF4) targets in myeloma vs. mature B lymphocyte, and Reactome runt-related transcription factor 3 (RUNX3). Among the selected SNPs, rs11230563 (R225W) showed missense mutation and low binding affinity with different food components in the autodock analysis. Glycyrrhizin, physalin B, janthitrem F, and casuarinin lowered it in only wild CD6 protein but not in mutated CD6. Plastoquinone 8, solamargine, saponin D, and matesaponin 2 decreased energy binding affinity in mutated CD6 proteins. The PRS of the 5-SNP and 6-SNP models exhibited a positive association with DU risk (OR = 3.14). The PRS of the 5-SNP PRS model interacted with irregular eating habits and smoking status. In participants with irregular eating habits or smokers, DU incidence was much higher in the participants with high PRS than in those with low PRS. In conclusion, the genetic impact of DU risk was mainly in regulating immunity, inflammation, and actin modification. Adults who are genetically susceptible to DU need to eat regularly and to be non-smokers. The results could be applied to personalize nutrition.
Self-Reported Coffee Consumption and Central and Peripheral Blood Pressure in the Cohort of the Brisighella Heart Study
Authors: Cicero Arrigo F. G. , Fogacci Federica , D’Addato Sergio , Grandi Elisa , Rizzoli Elisabetta , Borghi Claudio ,   on behalf of the Brisighella Heart Study
Published: January 2023

Even though coffee consumption has been clearly related to a number of benefits to the cardiovascular system, its effect on blood pressure (BP) has not been fully elucidated. In this sub-analysis of the Brisighella Heart Study (BHS), we compared central and peripheral BP values in a sub-cohort of 720 men (47.9%) and 783 women (52.1%) reporting the drinking of different amounts of coffee each day, for whom a full set of clinical, laboratory and hemodynamic parameters was available. According to our observations, moderate coffee drinking was associated to either higher levels of systolic BP (SBP) compared to those with heavy coffee consumption or lower SBP than that in the non-coffee drinking group (p-value for trend <0.05). In particular, people who drank 2 cups of coffee per day and people who drank >3 cups per day had lower SBP than non-coffee drinkers by 5.2 ± 1.6 mmHg (p = 0.010) and 9.7 ± 3.2 mmHg, respectively (p = 0.007). Similar trends were also observed for peripheral pulse pressure (PP), aortic BP and aortic PP. In the age-adjusted multiple linear regression model, negative predictors of SBP, PP, aortic BP and aortic PP were the estimated glomerular filtration rate (eGFR), female sex and coffee consumption. Positive predictors included body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C). Then, our findings show that regular coffee drinking is associated with lower SBP, PP, aortic BP and aortic PP, but with similar arterial stiffness.
Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women
Authors: Siblini Hiba , Al-Hendy Ayman , Segars James , González Frank , Taylor Hugh S. , Singh Bhuchitra , Flaminia Ainna , Flores Valerie A. , Christman Gregory M. , Huang Hao , Johnson Jeremy J. , Zhang Heping
Published: January 2023

A similar abstract of the interim analysis was previously published in Fertility and Sterility. EPIGALLOCATECHIN GALLATE (EGCG) FOR TREATMENT OF UNEXPLAINED INFERTILITY ASSOCIATED WITH UTERINE FIBROIDS (PRE-FRIEND TRIAL): EARLY SAFETY ASSESSMENT. Uterine fibroids are the most common cause of unexplained infertility in reproductive-aged women. Epigallocatechin gallate (EGCG), a green tea catechin, has demonstrated its ability to shrink uterine fibroids in prior preclinical and clinical studies. Hence, we developed an NICHD Confirm-funded trial to evaluate the use of EGCG for treating women with fibroids and unexplained infertility (FRIEND trial). Prior to embarking on that trial, we here conducted the pre-FRIEND study (NCT 04177693) to evaluate the safety of EGCG in premenopausal women. Specifically, our aim was to assess any adverse effects of EGCG alone or in combination with an ovarian stimulator on serum liver function tests (LFTs) and folate level. In this randomized, open-label prospective cohort, participants were recruited from the FRIEND-collaborative clinical sites: Johns Hopkins University, University of Chicago, University of Illinois at Chicago, and Yale University. Thirty-nine women, ages ≥18 to ≤40 years, with/without uterine fibroids, were enrolled and randomized to one of three treatment arms: 800 mg of EGCG daily alone, 800 mg of EGCG daily with clomiphene citrate 100 mg for 5 days, or 800 mg of EGCG daily with Letrozole 5 mg for 5 days. No subject demonstrated signs of drug induced liver injury and no subject showed serum folate level outside the normal range. Hence, our data suggests that a daily dose of 800 mg of EGCG alone or in combination with clomiphene citrate or letrozole (for 5 days) is well-tolerated and is not associated with liver toxicity or folate deficiency in reproductive-aged women.
High Consumption of Sugar-Sweetened Beverages Is Associated with Low Bone Mineral Density in Young People: The Brazilian Birth Cohort Consortium
Authors: Bragança Maylla Luanna Barbosa Martins , Bogea Eduarda Gomes , de Almeida Fonseca Viola Poliana Cristina , dos Santos Vaz Juliana , Confortin Susana Cararo , Menezes Ana Maria Baptista , Gonçalves Helen , Bettiol Heloisa , Barbieri Marco Antonio , Cardoso Viviane Cunha , da Silva Antônio Augusto Moura
Published: January 2023

Sugar-sweetened beverages (SSB) consumption may be associated with a reduction in bone mineral density (BMD). The aim of this study was to evaluate the association between the consumption of SSB and BMD among young people. We performed a cross-sectional study that evaluated 6620 young people (18–23 years of age) from three Brazilian birth cohorts (Ribeirão Preto, Pelotas, and São Luís). We analyzed the daily frequency and the amount and energy contribution of the SSB, which were obtained through a food frequency questionnaire. Total body and lumbar spine BMD (g/cm2), measured by dual-energy X-ray absorptiometry, were the outcomes. Unadjusted linear regression models, adjusted for sex, socioeconomic class, physical activity, smoking, alcohol consumption, and body mass index were used. The highest tertile of SSB consumption frequency (2.1–16.7 times/day) was associated with a lower lumbar spine BMD (β = −0.009; 95% CI: −0.017; −0.001; standardized β = −0.03). This association persisted after adjustment for confounders (β = −0.008; 95% CI: −0.016; −0.001; standardized β = −0.03). No association was observed between SSB consumption frequency and total body BMD or between the amount and energy contribution of SSB and total body or lumbar spine BMD. A high frequency of SSB consumption was associated with a low lumbar spine BMD.
Improving Functioning of Children Birth to Five with Emotional and Behavioral Problems: The Role of Comprehensive Mental Health Services and Supports
Authors: Cohen Alison K. , Hazelton Tracy , Bassey Henrissa , Gutierrez-Padilla Margie , Novosel Carolyn , Nichols Chloe R. , Jain Sonia
Published: January 2023

Introduction: Emotional and behavioral problems are growing among children ages birth to five, and racial/ethnic and socioeconomic disparities exist. Comprehensive, culturally responsive, family-driven systems of care, such as the one operated by California’s diverse, urban Alameda County, offer one potential intervention. Methods: We used client-level service data (n = 496 children) to calculate descriptive statistics and regression analyses (including multilevel models to account for observations for the same client at multiple points in time). We estimated the prevalence of mental health issues and assessed the association between the length of time using services and emotional and behavioral functioning. Results: Comprehensive mental health services and supports were associated with improved emotional and behavioral functioning outcomes for children over time, even after controlling for other risk factors. Discussion: Systems of care appear to support the multidimensional functioning of children and their families.
Supporting the Wound Healing Process—Curcumin, Resveratrol and Baicalin in In Vitro Wound Healing Studies
Authors: Jagiełło Kacper , Uchańska Oliwia , Matyja Konrad , Jackowski Mateusz , Wiatrak Benita , Kubasiewicz-Ross Paweł , Karuga-Kuźniewska Ewa
Published: January 2023

The purpose of the investigation was to evaluate the effect of the selected bioflavonoids curcumin, resveratrol and baicalin on the wound healing process in an in vitro model. In the study, Balb3t3 and L929 cell lines were used. The first step was the evaluation of the cytotoxicity of the substances tested (MTT assay). Then, using the scratch test (ST), the influence of bioflavonoids on the healing process was evaluated in an in vitro model. The second stage of the work was a mathematical analysis of the results obtained. On the basis of experimental data, the parameters of the Brian and Cousens model were determined in order to determine the maximum value of the cellular and metabolic response that occurs for the examined range of concentrations of selected bioflavonoids. In the MTT assays, no cytotoxic effect of curcumin, resveratrol and baicalin was observed in selected concentrations, while in the ST tests for selected substances, a stimulatory effect was observed on the cell division rate regardless of the cell lines tested. The results obtained encourage further research on the use of substances of natural origin to support the wound healing process.
Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir
Authors: Alchikh Maren , Obermeier Patrick E. , Schweiger Brunhilde , Rath Barbara A.
Published: January 2023

In 2019, EMA licensed intravenous (IV) zanamivir for severe influenza virus infection in children over 6 months as well as adults. Prior to that, it was possible via a compassionate use program. We present successful compassionate use of IV zanamivir in a 14-year-old female with severe influenza A(H3N2) and multi-organ failure, who had failed oral oseltamivir. Her illness was complicated by acute respiratory distress syndrome and rhabdomyolysis requiring extracorporeal membrane oxygenation and hemofiltration. Considering the broad safety margins with neuraminidase inhibitors, an adult dose of 600 mg IV BID was administered in this 60 kg patient. Influenza virus was cleared rapidly and undetectable on day 13. Creatine kinase (CK) values were dropping from 38,000 to 500 within nine days. Given the recent licensure of IV zanamivir, multi-center prospective observational studies in pediatric Intensive Care Unit patients would be beneficial to guide the most appropriate use of IV zanamivir in this vulnerable age group.
Targeting the Interplay of Autophagy and ROS for Cancer Therapy: An Updated Overview on Phytochemicals
Authors: Dong Lixia , He Jingqiu , Luo Li , Wang Kui
Published: January 2023

Autophagy is an evolutionarily conserved self-degradation system that recycles cellular components and damaged organelles, which is critical for the maintenance of cellular homeostasis. Intracellular reactive oxygen species (ROS) are short-lived molecules containing unpaired electrons that are formed by the partial reduction of molecular oxygen. It is widely known that autophagy and ROS can regulate each other to influence the progression of cancer. Recently, due to the wide potent anti-cancer effects with minimal side effects, phytochemicals, especially those that can modulate ROS and autophagy, have attracted great interest of researchers. In this review, we afford an overview of the complex regulatory relationship between autophagy and ROS in cancer, with an emphasis on phytochemicals that regulate ROS and autophagy for cancer therapy. We also discuss the effects of ROS/autophagy inhibitors on the anti-cancer effects of phytochemicals, and the challenges associated with harnessing the regulation potential on ROS and autophagy of phytochemicals for cancer therapy.
PPAR Gamma Agonist Leriglitazone Recovers Alterations Due to Pank2-Deficiency in hiPS-Derived Astrocytes
Authors: Santambrogio Paolo , Cozzi Anna , Di Meo Ivano , Cavestro Chiara , Vergara Cristina , Rodríguez-Pascau Laura , Martinell Marc , Pizcueta Pilar , Tiranti Valeria , Levi Sonia
Published: January 2023

The novel brain-penetrant peroxisome proliferator-activated receptor gamma agonist leriglitazone, previously validated for other rare neurodegenerative diseases, is a small molecule that acts as a regulator of mitochondrial function and exerts neuroprotective, anti-oxidative and anti-inflammatory effects. Herein, we tested whether leriglitazone can be effective in ameliorating the mitochondrial defects that characterize an hiPS-derived model of Pantothenate kinase-2 associated Neurodegeneration (PKAN). PKAN is caused by a genetic alteration in the mitochondrial enzyme pantothenate kinase-2, whose function is to catalyze the first reaction of the CoA biosynthetic pathway, and for which no effective cure is available. The PKAN hiPS-derived astrocytes are characterized by mitochondrial dysfunction, cytosolic iron deposition, oxidative stress and neurotoxicity. We monitored the effect of leriglitazone in comparison with CoA on hiPS-derived astrocytes from three healthy subjects and three PKAN patients. The treatment with leriglitazone did not affect the differentiation of the neuronal precursor cells into astrocytes, and it improved the viability of PKAN cells and their respiratory activity, while diminishing the iron accumulation similarly or even better than CoA. The data suggest that leriglitazone is well tolerated in this cellular model and could be considered a beneficial therapeutic approach in the treatment of PKAN.
Microfluidic Manipulation for Biomedical Applications in the Central and Peripheral Nervous Systems
Authors: Li Zhenghang , Jiang Zhenmin , Lu Laijin , Liu Yang
Published: January 2023

Physical injuries and neurodegenerative diseases often lead to irreversible damage to the organizational structure of the central nervous system (CNS) and peripheral nervous system (PNS), culminating in physiological malfunctions. Investigating these complex and diverse biological processes at the macro and micro levels will help to identify the cellular and molecular mechanisms associated with nerve degeneration and regeneration, thereby providing new options for the development of new therapeutic strategies for the functional recovery of the nervous system. Due to their distinct advantages, modern microfluidic platforms have significant potential for high-throughput cell and organoid cultures in vitro, the synthesis of a variety of tissue engineering scaffolds and drug carriers, and observing the delivery of drugs at the desired speed to the desired location in real time. In this review, we first introduce the types of nerve damage and the repair mechanisms of the CNS and PNS; then, we summarize the development of microfluidic platforms and their application in drug carriers. We also describe a variety of damage models, tissue engineering scaffolds, and drug carriers for nerve injury repair based on the application of microfluidic platforms. Finally, we discuss remaining challenges and future perspectives with regard to the promotion of nerve injury repair based on engineered microfluidic platform technology.
Development of Synthetic mRNAs Encoding Split Cytotoxic Proteins for Selective Cell Elimination Based on Specific Protein Detection
Authors: Free Kendall , Nakanishi Hideyuki , Itaka Keiji
Published: January 2023

For the selective elimination of deleterious cells (e.g., cancer cells and virus-infected cells), the use of a cytotoxic gene is a promising approach. DNA-based systems have achieved selective cell elimination but risk insertional mutagenesis. Here, we developed a synthetic mRNA-based system to selectively eliminate cells expressing a specific target protein. The synthetic mRNAs used in the system are designed to express an engineered protein pair that are based on a cytotoxic protein, Barnase. Each engineered protein is composed of an N- or C-terminal fragment of Barnase, a target protein binding domain, and an intein that aids in reconstituting full-length Barnase from the two fragments. When the mRNAs are transfected to cells expressing the target protein, both N- and C-terminal Barnase fragments bind to the target protein, causing the intein to excise itself and reconstitute cytotoxic full-length Barnase. In contrast, when the target protein is not present, the reconstitution of full-length Barnase is not induced. Four candidate constructs containing split Barnase were evaluated for the ability to selectively eliminate target protein–expressing cells. One of the candidate sets demonstrated highly selective cell death. This system will be a useful therapeutic tool to selectively eliminate deleterious cells.