bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer
Authors: Miller Richard A , Luke Jason John , Hu Shenshen , Mahabhashyam Suresh , Jones William B , Marron Thomas , Merchan Jaime R , Hughes Brett G M , Willingham Stephen B
Published: December 2022

Background

CD73 is widely expressed on immune cells playing a critical role in immunomodulatory functions including cell adhesion and migration, as a costimulatory molecule for T cells and in production of adenosine. The function of CD73 expressed on B cells has not been fully characterized. Mupadolimab is an anti-human CD73 antibody that activates B cells. We evaluated the characteristics of this antibody and its effects on immune cells in vitro and in vivo.

Methods

Mupadolimab binding to CD73, inhibition of CD73 enzymatic activity, and effects on lymphocyte activation were evaluated in vitro by measuring changes in immunophenotype by flow cytometry. Cryogenic-transmission electron microscopy was used to determine epitope binding. Effects on human B cells in vivo were evaluated in immunodeficient NSG-SGM3 mice immunized with SARS-CoV-2 and influenza viral antigens. Safety and immune effects were evaluated in the completed dose escalation portion of a phase 1 trial conducted in patients with cancer.

Results

Mupadolimab binds to a unique epitope on CD73POSB cells resulting in their activation and differentiation through B cell receptor signaling pathways. Mupadolimab induces expression of CD69, CD83, CD86 and MHC class II on B cells along with morphological transformation into plasmablasts and expression of CD27, CD38 and CD138. These effects are independent of adenosine. Mupadolimab binds to the N-terminal of CD73 in the closed position and competitively inhibits substrate binding. Mupadolimab enhanced antigen specific antibody response to SARS-CoV-2 spike protein and influenza hemagglutinin in humanized mouse models. Mupadolimab was evaluated as a monotherapy in a phase 1 trial (NCT03454451) in 34 patients with advanced cancer and demonstrated binding to CD73POScirculating cells and transient reduction in the number of B cells, with return of CD73NEGB cells with memory phenotype. No dose-limiting toxicities or changes in serum immunoglobulins were seen.

Conclusions

Mupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69POSB cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant.

Trial registration number

NCT03454451.
Predictors of perceived risk in first-degree relatives of patients with rheumatoid arthritis
Authors: Bunnewell Sarah , Wells Imogen , Zemedikun Dawit , Simons Gwenda , Mallen Christian D , Raza Karim , Falahee Marie
Published: December 2022

Objectives

To define variables associated with perceived risk of developing rheumatoid arthritis (RA) in first-degree relatives (FDRs) of patients with RA.

Methods

Patients with RA and their FDRs were invited to complete cross-sectional surveys. FDR and index patient responses were linked. FDRs’ perceived absolute risk, comparative risk, experiential risk and worry about risk were assessed using 5-point Likert scales. FDR predictor variables included demographics, illness perceptions and psychosocial variables. Patient predictors of FDR perceived risk were assessed. Binary logistic regression examined the relationship between FDR characteristics and perceived risk of RA. Generalised estimating equations assessed whether patient variables predicted FDR’s perceived risk.

Results

396 FDRs returned a survey. 395 FDRs provided sufficient data and were included in analysis. Paired data from 213 patients were available for 291 of these FDRs. All measures of perceived risk were inter-correlated. 65.2% of FDRs perceived themselves to be ‘likely’ or ‘very likely’ to develop RA in their lifetime. Relationship with index patient, high health anxiety, female gender, long perceived RA duration, high perceived concern about RA, negative perceived emotional impact of RA and low perceptions of how well treatment would control RA were all associated with increased FDRs’ perceived risk. Patient characteristics did not associate with FDRs’ risk perceptions.

Conclusions

FDRs’ perceived risk of RA was high. Key predictors included being a child of a patient with RA, higher health anxiety and lower perceptions of RA treatment control. An understanding of these predictors will inform the development of tailored risk communication resources and preventive clinical strategies for RA.
Dysphagia is associated with worse clinical outcomes in geriatric trauma patients
Authors: Kregel Heather R , Attia Mina , Pedroza Claudia , Meyer David E , Wandling Michael W , Dodwad Shah-Jahan M , Wade Charles E , Harvin John A , Kao Lillian S , Puzio Thaddeus J
Published: December 2022

Introduction

Dysphagia is associated with increased morbidity, mortality, and resource utilization in hospitalized patients, but studies on outcomes in geriatric trauma patients with dysphagia are limited. We hypothesized that geriatric trauma patients with dysphagia would have worse clinical outcomes compared with those without dysphagia.

Methods

Patients with and without dysphagia were compared in a single-center retrospective cohort study of trauma patients aged ≥65 years admitted in 2019. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) length of stay (LOS), hospital LOS, discharge destination, and unplanned ICU admission. Multivariable regression analyses and Bayesian analyses adjusted for age, Injury Severity Score, mechanism of injury, and gender were performed to determine the association between dysphagia and clinical outcomes.

Results

Of 1706 geriatric patients, 69 patients (4%) were diagnosed with dysphagia. Patients with dysphagia were older with a higher Injury Severity Score. Increased odds of mortality did not reach statistical significance (OR 1.6, 95% CI 0.6 to 3.4, p=0.30). Dysphagia was associated with increased odds of unplanned ICU admission (OR 4.6, 95% CI 2.0 to 9.6, p≤0.001) and non-home discharge (OR 5.2, 95% CI 2.4 to 13.9, p≤0.001), as well as increased ICU LOS (OR 4.9, 95% CI 3.1 to 8.1, p≤0.001), and hospital LOS (OR 2.1, 95% CI 1.7 to 2.6, p≤0.001). On Bayesian analysis, dysphagia was associated with an increased probability of longer hospital and ICU LOS, unplanned ICU admission, and non-home discharge.

Conclusions

Clinically apparent dysphagia is associated with poor outcomes, but it remains unclear if dysphagia represents a modifiable risk factor or a marker of underlying frailty, leading to poor outcomes. This study highlights the importance of screening protocols for dysphagia in geriatric trauma patients to possibly mitigate adverse outcomes.

Level of evidence

Level III.
The effects of oil spill dispersant use on marine birds: a review of scientific literature and identification of information gaps
Authors: Osborne Orla E. , Willie Megan M.C. , O’Hara Patrick D.
Published: December 2022

Dispersants, a class of chemical spill-treating agents used to treat oil spills, are commonly used globally as an alternative response measure. Applying dispersants to an oil slick, shortly after the spill has occurred, can protect shoreline environments and sea surface-dwelling animals, such as some marine bird species, limiting individuals or local populations from the consequences of coming into contact with large quantities of oil. However, this benefit comes with the cost of increasing oil exposure risk to marine biota that spend time in the water column. It is generally believed that the benefits of dispersant use outweigh the costs under most circumstances. However, it is rarely acknowledged that the use of dispersants may have negative impacts on marine biota at the individual or local population level, including marine birds. In Canada, Corexit EC9500A, a regulated dispersant, is being proposed for expanded use beyond treating spills from an offshore oil and gas facility. To understand what the potential impacts from dispersant use are to marine birds, we conducted a literature review to identify the direct and indirect effects of their use. We also provide oil spill responders with a Pathway of Effects (POE) conceptual model, a tool for understanding the interactions between dispersants, marine birds, and their environment to support a holistic consideration as part of the oil spill response decision-making process. Fundamental uncertainties remain, however, and if left unaccounted for in the decision-making process, they may compromise the appropriateness of spill response approaches and outcomes. We recommend that oil spill responders incorporate the known benefits and costs of dispersant use on marine birds into a decision-making framework such as a Net Environmental Benefit Analysis (NEBA) and with consideration of the POE concept models provided. These recommendations are particularly relevant where a decision-making framework such as NEBA is becoming a more standardized component of the response process. Additionally, greater investment in lab and field-based research, and field observations through monitoring, is required to address existing decision-making uncertainties and provide information gap closure.
Generating mobility networks with generative adversarial networks
Authors: Mauro Giovanni , Luca Massimiliano , Longa Antonio , Lepri Bruno , Pappalardo Luca
Published: December 2022

The increasingly crucial role of human displacements in complex societal phenomena, such as traffic congestion, segregation, and the diffusion of epidemics, is attracting the interest of scientists from several disciplines. In this article, we address mobility network generation, i.e., generating a city’s entire mobility network, a weighted directed graph in which nodes are geographic locations and weighted edges represent people’s movements between those locations, thus describing the entire mobility set flows within a city. Our solution is MoGAN, a model based on Generative Adversarial Networks (GANs) to generate realistic mobility networks. We conduct extensive experiments on public datasets of bike and taxi rides to show that MoGAN outperforms the classical Gravity and Radiation models regarding the realism of the generated networks. Our model can be used for data augmentation and performing simulations and what-if analysis.
Location Problems with Cutoff
Authors: Müller Raoul , Schöbel Anita , Schuhmacher Dominic
Published: December 2022

In this paper, we study a generalized version of the Weber problem of finding a point that minimizes the sum of its distances to a finite number of given points. In our setting, these distances may be cut off at a given value [Formula: see text], and we allow for the option of an empty solution at a fixed cost [Formula: see text]. We analyze under which circumstances these problems can be reduced to the simpler Weber problem, and also when we definitely have to solve the more complex problem with cutoff.

We furthermore present adaptions of the algorithm of Drezner, Mehrez and Wesolowsky (1991 [The facility location problem with limited distances. Transportation Science, 25(3), 183–187, INFORMS]) to our setting, which in certain situations are able to substantially reduce computation times as demonstrated in a simulation study. The sensitivity with respect to the cutoff value is also studied, which allows us to provide an algorithm that efficiently solves the problem simultaneously for all [Formula: see text].
ON THE CONSTRUCTION OF (p,k)-HYPERGEOMETRIC FUNCTION AND APPLICATIONS
Authors: HE FULI , BAKHET AHMED , HIDAN MUAJEBAH , ABD-ELMAGEED HALA
Published: December 2022

In this paper, we construct a [Formula: see text]-hypergeometric function by using the Hadamard product, which we call the generalized [Formula: see text]-hypergeometric function. Several properties, namely, convergence properties, derivative formulas, integral representations and differential equations are indicated of this function. The latter function is a generalization of the usual hypergeometric function, the k-analogue of hypergeometric function and other hypergeometric functions are recently presented. As an application, we obtain the solution of the generalized fractional kinetic equations involving of the generalized [Formula: see text]-hypergeometric function.
The Polynomial Modules over Quantum Group Uq(sl3)
Authors: Xia Limeng , Cai Qianqian , Zhang Jiao
Published: December 2022

Let [Formula: see text] be a finite dimensional complex simple Lie algebra with Cartan subalgebra [Formula: see text]. Then [Formula: see text] has a [Formula: see text]-module structure if and only if [Formula: see text] is of type [Formula: see text] or of type [Formula: see text]; this is called the polynomial module of rank one. In the quantum version, the rank one polynomial modules over [Formula: see text] have been classified. In this paper, we prove that the quantum group [Formula: see text] has no rank one polynomial module.
Syntheses, characterizations, and properties of 1,4-phenylene and 4,4′-biphenylene bridged BOBPY dimers
Authors: Wang Jun , Zuo Huiquan , Wu Qinghua , Hao Erhong , Jiao Lijuan
Published: December 2022

Two novel phenylenes (1,4-phenylene and 4,4′-biphenylene) bridged dimeric BOBPY (Boron complexed [Formula: see text]O-type benzopyrromethenes) were designed and synthesized from the one-pot condensation of pyrrole with formylisoindole and subsequent complexation with diboronic acid. These novel dyes were fully characterized by NMR spectroscopy, HRMS, absorption and fluorescence emission spectroscopy, and cyclic voltammetry. These resulting BOBPY dimers are highly photostable and show intense absorption and emission in the region of 618 to 644 nm with high absorption coefficients and solvent-dependent fluorescence quantum yields. The electronic interactions between BOBPY units are related with length of the linker. And the dimer with short 1,4-phenylene linker was more sensitive to the polarity of the solvents than that of the other dimer, suggesting that the short linkage allowed stronger electronic communication between the two BOBPY units.
Zn(II) phthalocyanines having fluoroether groups: Synthesis, characterization, photo-physicochemical and biological properties
Authors: Harmandar Kevser , Gonca Serpil , Küçük Tuğba , Günay Aysel , Atilla Devrim , Özdemir Sadin , Gürek Ayşe Gül
Published: December 2022

Tetra non-peripheral and peripheral substituted Zn(II) phthalocyanine (Pc) derivatives bearing 2,2-difluoro-2-[1,1,2,2-tetrafluoro-2-(trifluoromethoxy)ethoxy]ethoxy groups (KH-69, KH-71) were synthesized and characterized to be antioxidant and antimicrobial agents. Photo-physicochemical properties of these compounds were investigated. Then, the DPPH free radical scavenging activity of the Pc derivatives was found as 97.74% and 94.89%, respectively. Both the Pc complexes showed perfect DNA nuclease activity with double strain break against pBR 322 plasmid DNA at 100 mg/L concentration. KH-69 and KH-71 indicated good antimicrobial activity against studied Gram-positive and Gram-negative bacteria, and fungal strains. Moreover, the Pcs showed excellent cell viability inhibition activity even at the lowest concentration. These Pc derivatives inhibited P. aeroginasa and S. aureus biofilm formation. The Pcs showed the highest biofilm inhibition with photodynamic therapy against S. aureus and P. aeroginasa with 95.40% and 90.03%, respectively.
Quantum entangled connectivity and functional connectivity of human brain
Authors: Zhai You , Qiu Linjie , He Chenxiang , Wang Lina , Zhai Jian
Published: December 2022

Quantum process may conduce to brain function. Particularly, it was proposed that the Posner molecules, Cag(PO4)6, can serve as neural qubits, which can maintain quantum entanglement between phosphorus nuclei for quite a long time. We study the process from entangled Posner molecules to the synchronized activities of brain. A diffusion model of Posner molecules with appropriate boundary conditions and the mean first arriving time of Posner molecules from one area of brain to another are obtained. We establish linkages between the quantum entangled connectivity of brain and the remaining time of entangled Posner molecules before decoherence. Based on these results, we find direct correlations between entangled Posner molecules and the functional connectivity of human brain. Furthermore, we discover that the quantum entangled connectivity depends on age.
The Development of Emergency Communication Device for Tianwen-1 Probe
Authors: Wang Yin , Luo Qing
Published: December 2022

Mars is one of the most valuable planets for space exploration. After entering the entry descent and landing (EDL) phase, the spacecraft would carry out a series of procedural deceleration operations and achieve soft landing on the surface of Mars. In the process of EDL, the landing platform would encounter a series of irreversible incidents within environmental unpredictability, making this process highly risky. The emergency communication device plays an important role if in the Mars Exploration Program. It can capture and store key dynamic parameters during EDL phase, enabling a high probability of survival in the occurrence of a faulty condition. It can also send the stored data to the Mars obit probe when the communication condition is met. This paper presents a scheme design for the emergency communication device based on its functionality and performance requirements. It includes the design proposal, simulation results, reliability analysis, technical risks and control measures, inheritance and performance compliance which verifies the rationality and correctness of the design.
Experimental study of the effect of bound water on the shear strength and structural units of Malan loess
Authors: Hao Zhitao , Li Xi'an , Gao Rongrong , Hu Wei , Zhang Jing , He Jun
Published: December 2022

The structural specificity and hydrological sensitivity of loess have a big impact on its strength, deformation and long-term stability and safety. This topic is being actively researched, and focuses on the macromechanical behaviour of the shear strength of loess and its micromechanisms from the perspective of bound water. In this study, based on the combined determination of isothermal adsorption and the liquid–plastic limit, bound water is analysed qualitatively and quantitatively, and the entire humidity sequence is divided in a new method. The shear strength of Malan loess measured by the direct shear test is also analysed to investigate the relationship between bound water, shear strength and basic structural units. The results show that the adsorption patterns for the Malan loess in the three regions studied are approximately the same but, at the same humidity, their maximum moisture content (
W
мг
) was, from highest to lowest, 7.13% in Chan he, 6.54% in Yan'an and 5.54% in Hei fang tai, which is related to clay minerals and their contents in the soil. In addition, the change in strength of the loess is divided into three stages using the maximum moisture content (
W
мг
) and plastic limit (
W
P
) as the characteristic moisture content. The patterns of strength change for the loess in the three regions is similar throughout the moisture content sequence: all stages show a negative correlation between moisture content and shear strength but the internal mechanism of each stage is not the same due to the different connection forces between the basic structural units of the loess. The change in bound water content caused by the cementation of glue and clay particles also yields certain changes in cohesion, which is linearly fitted to the shear strength and its parameters. Finally, the bound water in the soil changes the microstructure of the soil, and determines the combination characteristics and contact mode of the ‘core clothes’ in the microagglomerate structure of the loess. This study describes the essence of soil–water structural interactions and provides theoretical references for applications in geotechnical engineering fields such as slope protection and road construction.
The construction of the HADES underground research laboratory and its role in the development of the Belgian concept of a deep geological repository
Authors: Li Xiangling , Neerdael Bernard , Raymaekers Didier , Sillen Xavier
Published: December 2022

When the Belgian Nuclear Research Centre (SCK CEN) launched a research, development and demonstration programme on geological disposal in the 1970s, it was not certain if a deep geological repository could be constructed in poorly indurated clay. This was tested by constructing the HADES underground research laboratory (URL) in Boom Clay, 225 m below SCK CEN's site in Mol. The construction history of the URL reflects how the understanding of the Boom Clay increased and how the excavation techniques and design of the gallery lining improved. It demonstrated that shafts, galleries and crossings between galleries can be constructed using industrial techniques. It also allowed characterization of the hydromechanical response of the clay and the clay disturbances induced by the excavation. This increased understanding is also reflected in the evolution of the geological disposal concept considered in Belgium. The current disposal concept foresees the installation of seals in the shafts and galleries. The HADES URL also offered the opportunity to test possible seal designs and develop a better understanding of the behaviour of bentonite, a possible seal material, owing to its swelling capacity, under
in situ
conditions.
Interlacing Rod and Sphere Morphology of MnO2 in RGO/NiO/MnO2 Ternary Nanocomposites for Supercapacitive Applications
Authors: P. Joselene Suzan Jennifer , S. Muthupandi , Joe Raja Ruban M. , Madhavan J. , Prathap S. , S. R. Niranjana , M. Victor Antony Raj
Published: December 2022

Supercapacitors are promising energy storage devices. Herein a comparative study was carried out between two samples of reduced graphene oxide-infused binary metal oxides, in which the morphology of one of the metal oxides (Manganese oxide) is altered. MnO2 was synthesized in two morphologies namely nanorods and nanospheres. The two morphologies (rod and spheres) were separately composited with the as-synthesized cone-structured nickel oxide and sheets of reduced graphene oxide (rGO) and were subjected to various structural, functional, morphological, electrochemical characterizations etc. The morphologies and structures of the as prepared samples were characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy and X-ray photoelectron spectrometer (XPS). The functional properties were determined using Fourier Transform Infra-Red (FTIR) Spectroscopy. The electrochemical performance of both the samples were analysed using Cyclic Voltammetry (CV), Galvanostatic Charge/Discharge (GCD) measurements and Electrochemical Impedance Spectroscopy (EIS) under electrolytes with different pH namely 1M Na2SO4(pH = 7) and 1M Na2CO3(pH = 11). The CV was analysed with different scan rates and GCD was taken under 1–5 Ag−1 current densities. The cycling stability of the materials were testified for 5000 cycles of CV and GCD. The results are discussed. The main advantage of this work is that the best suited morphology with better ion transfer rate having commendable electrochemical ability and long-standing cycle rate for a promising supercapacitor is identified which will serve as the reference for the future supercapacitor electrodes.
Distribution Characteristics of Multiphysics around the Bubble on the Surface of Photoelectrode
Authors: Cao Zhenshan , Feng Yuyang , Zhang Bo , Xu Qiang , Wang Yechun , Guo Liejin
Published: December 2022

In the heterogeneous photocatalytic reaction systems, the evolution of bubbles on the catalyst surface is a complex process that depends on multiple factors, such as the solid–liquid interface structure, solution properties of the reaction system, and multiphysics interactions, and directly affects energy and mass transport processes. This study investigated the multiphysics distribution around a bubble and the bubble detachment characteristics on the surface of a TiO2 photoelectrode during photoelectrocatalytic water splitting. The bubble diameter had an effect on the distribution of the light field in the system, affecting the temperature and flow distributions of the electrolyte around the bubble. Marangoni convection was induced by the inhomogeneous temperature distribution along the bubble interface, which enhanced the heat and mass transfer near the reaction site. It was also demonstrated that an increase in laser power increased Marangoni convection on the bubble surface, thus delaying bubble detachment. A force model for predicting the bubble detachment diameter that considered the coupling effect between the light, temperature, and flow fields was developed. The predicted bubble detachment diameters agreed well with the experimental results within an error of ±10%.
A compartmentalized mathematical model of the β1- and β2-adrenergic signaling systems in ventricular myocytes from mouse in heart failure
Authors: Asfaw Tesfaye Negash , Bondarenko Vladimir E.
Published: December 2022

Mouse models of heart failure are extensively used to research human cardiovascular diseases. In particular, one of the most common is the mouse model of heart failure resulting from transverse aortic constriction (TAC). Despite this, there are no comprehensive compartmentalized mathematical models that describe the complex behavior of the action potential, [Ca2+]i transients, and their regulation by β1- and β2-adrenergic signaling systems in failing mouse myocytes. In this paper, we develop a novel compartmentalized mathematical model of failing mouse ventricular myocytes after TAC procedure. The model describes well the cell geometry, action potentials, [Ca2+]i transients, and β1- and β2-adrenergic signaling in the failing cells. Simulation results obtained with the failing cell model are compared with those from the normal ventricular myocytes. Exploration of the model reveals the sarcoplasmic reticulum Ca2+ load mechanisms in failing ventricular myocytes. We also show a larger susceptibility of the failing myocytes to early and delayed afterdepolarizations and to a proarrhythmic behavior of Ca2+ dynamics upon stimulation with isoproterenol. The mechanisms of the proarrhythmic behavior suppression are investigated and sensitivity analysis is performed. The developed model can explain the existing experimental data on failing mouse ventricular myocytes and make experimentally testable predictions of a failing myocyte’s behavior.
Bioinformatic tools for epitranscriptomics
Authors: Taguchi Y.-H.
Published: December 2022

The epitranscriptome, defined as RNA modifications that do not involve alterations in the nucleotide sequence, is a popular topic in the genomic sciences. Because we need massive computational techniques to identify epitranscriptomes within individual transcripts, many tools have been developed to infer epitranscriptomic sites as well as to process datasets using high-throughput sequencing. In this review, we summarize recent developments in epitranscriptome spatial detection and data analysis and discuss their progression.
The evolutionarily conserved hif-1/bnip3 pathway promotes mitophagy and mitochondrial fission in crustacean testes during hypoxia
Authors: Zhao Qianqian , Sun Xichao , Zheng Cheng , Xue Cheng , Jin Yiting , Zhou Na , Sun Shengming
Published: December 2022

The hypoxia-inducible factor 1 (HIF-1) cascade is an ancient and strongly evolutionarily conserved signaling pathway that is involved in the hypoxic responses of most metazoans. Despite immense advances in the understanding of the HIF-1-mediated regulation of hypoxic responses in mammals, the contribution of the hif-1 cascade in the hypoxic adaptation of nonmodel invertebrates remains unclear. In this study, we used the oriental river prawn Macrobrachium nipponense for investigating the roles of hif-1-regulated mitophagy in crustacean testes under hypoxic conditions. We identified that the Bcl-2/adenovirus E1B 19-kDa interacting protein (bnip3) functions as a regulator of mitophagy in M. nipponense and demonstrated that hif-1α activates bnip3 by binding to the bnip3 promoter. Hif-1α knockdown suppressed the expression of multiple mitophagy-related genes, and prawns with hif-1α knockdown exhibited higher mortality under hypoxic conditions. We observed that the levels of BNIP3 were induced under hypoxic conditions and detected that bnip3 knockdown inhibited the mitochondrial translocation of dynamin-related protein 1 (drp1), which is associated with mitochondrial fission. Notably, bnip3 knockdown inhibited hypoxia-induced mitophagy and aggravated the deleterious effects of hypoxia-induced reactive oxygen species (ROS) production and apoptosis. The experimental studies demonstrated that hypoxia induced mitochondrial fission in M. nipponense via drp1. Altogether, the study elucidated the mechanism underlying hif-1/bnip3-mediated mitochondrial fission and mitophagy and demonstrated that this pathway protects crustaceans against ROS production and apoptosis induced by acute hypoxia.
Boundary Layer Resolving Exact Difference Scheme for Solving Singularly Perturbed Convection-Diffusion-Reaction Equation
Authors: Woldaregay Mesfin Mekuria , Duressa Gemechis File
Published: December 2022

This paper considers the numerical treatment of singularly perturbed time-dependent convection-diffusion-reaction equation. The diffusion term of the equation is multiplied by a small perturbation parameter (ε), which takes an arbitrary value in the interval (0, 1]. For small values of ε, the solution of the equation exhibits an exponential boundary layer which makes it difficult to solve it analytically or using classical numerical methods. We proposed numerical schemes using the Crank–Nicolson method in time derivative discretization and the nonstandard finite difference method (exact finite difference method) in space derivative discretization on a uniform and piecewise uniform Shishkin mesh. The existence of unique discrete solutions and the stability of the schemes are discussed and proved. Uniform convergence of the schemes is proved. The formulated schemes converge uniformly with linear order of convergence. The method on Shishkin mesh possesses boundary layer resolving property. We validated the methods by considering two numerical examples for different values of

ε

and mesh length.
Explosion Flame and Pressure Characteristics of Nonstick Coal Dust and the Inhibition of Explosion Suppressants
Authors: Liu Tianqi , Jia Ruiheng , Dong Xiaoting , Zhao Xuan , Tian Weiye , Cai Zhixin , Wang Ning
Published: December 2022

Nonstick coal is widely distributed in the world and is an important resource for human beings. The explosion characteristics and explosion suppression of nonstick coal dust are increasingly concerning. In this paper, the flame and pressure characteristics of a nonstick coal dust explosion are studied, and the suppression effect of SiO2, KCl, and NH4H2PO4 on the explosion is analyzed. It is concluded that the maximum propagation distance of a nonstick coal dust explosion flame is 0.59 m, the maximum pressure is 0.63 MPa, and the maximum pressure rise rate is 40.79 MPa/s. The explosion suppression effect of SiO2 is worse than that of KCl, but the inhibition effect of NH4H2PO4 is the best among the three kinds of explosion suppressants. When the mass percentage of NH4H2PO4 dust mixed with coal dust is 70%, the coal dust explosion is completely suppressed. It absorbs a certain amount of heat to promote the chemical reaction, which plays a certain role in controlling the explosion process, and its explosion suppression mechanism includes both physical and chemical explosion suppression.
A Review of the Research Progress of Motor Vibration and Noise
Authors: Wu Bo , Qiao Mingzhong
Published: December 2022

Motor vibration and noise is an important index to measure motor performance. How to reduce vibration and noise is one of the important topics in the field of motor design. Analysis, calculation, and reduction of motor vibration and noise have attracted more and more attention from motor designers. Based on the three main types of noise sources of motors, this paper firstly analyzes their causes and mechanisms and secondly introduces their main research methods. Although there are many summary articles on the research of motor vibration and noise, most of the theories and research methods on the causes of various kinds of noise are not comprehensive enough, lacking theoretical calculation and analysis, especially for mechanical noise and aerodynamic noise. This paper summarizes the research in the recent ten years, especially in the recent five years, with a view to providing a reference for the future development of this field.
Multiobjective Optimization Design of Truss Antenna
Authors: Wu Di , Ma Xiaofei , Chen Jinbao , Chen Chuanzhi , Zhao Jiang , Lin Kunyang
Published: December 2022

During the design and manufacturing process of the truss antenna, the surface accuracy of the truss antenna is inherently affected by tolerance. An appropriate optimal design of the truss antenna structure is important to improve surface accuracy. In order to receive the optimal design of the truss structure, this paper adopts the multiobjective optimization algorithm based on an approximate model to optimize the tolerance model with random error. Firstly, considering the influence of the processing and assembly errors of the members on the surface accuracy of the structure, the equilibrium state equation of the truss is established by the principle of minimum potential energy. Then, the relationship between the tolerance and the surface accuracy is obtained by the Monte Carlo method. For improving the computing efficiency of the Monte Carlo method, an approximate model of the truss antenna unit is established, where the rod length tolerance is set as the design variable, and the truss surface accuracy and processing cost are set as the objective functions. Finally, tolerance optimization is carried out by using the multiobjective genetic algorithm. The results indicate that the Pareto solution is obtained with an error less than 10%. Moreover, a set of solutions of the tolerance are obtained which can meet different antenna design requirements. And the results show that the influence of the web rod is significantly greater than that of the bottom rod on the surface accuracy of the structure.
Potential Wound Healing of PLGA Nanoparticles Containing a Novel L‐Carnitine–GHK Peptide Conjugate
Authors: Ramezanpour Sorour , Tavatoni Pedram , Akrami Mohammad , Navaei-Nigjeh Mona , Shiri Pezhman
Published: December 2022

The development of a product that has simultaneous wound healing, anti‐inflammatory, and antimicrobial properties is desirable for wound healing medicine. In this study, glycine–histidine–lysine (GHK) peptide as a skin repair accelerator was coupled to L‐carnitine with antibacterial and anti‐inflammatory properties to investigate its new wound healing properties in a nanoparticle (NP) platform. The conjugate was synthesized by solid‐phase synthesis method with Fmoc chemistry, purified by preparative HPLC, and was identified with ESI‐Mass technique. The conjugate was then loaded into PLGA NPs, which was prepared using solvent evaporation technique. Zetasizer results showed a mean size and zeta potential of 193.15 nm and −30.2 ± 3.8 mV for the conjugate‐loaded PLGA NPs. Scanning electron microscopy (SEM) exhibited spherical‐shaped morphology for the NPs with uniform size distribution (PDI = 0.265). Conjugate release from the NPs was about 10% at initial time, which increased to more than about 70% at 200 hr, exhibiting a sustained release trend. Additionally, the treatment of fibroblasts with the nanoconjugate indicated its biocompatibility. Compared to GHK, L‐carnitine and free conjugates, the most satisfactory wound healing activity was observed for conjugate‐loaded NPs upon wound closure in a rat model of skin injury repair. Furthermore, more epithelialization and neovascularization were observed for L‐carnitine–GHK nanoconjugate. Taken together, the L‐carnitine–GHK conjugate‐loaded PLGA NP will be a promising candidate for wound healing management.
A Comprehensive Update of Cerebral Organoids between Applications and Challenges
Authors: Li Xiaodong , Shopit Abdullah , Wang Jingmin
Published: December 2022

The basic technology of stem cells has been developed and created organoids, which have established a strong interest in regenerative medicine. Different cell types have been used to generate cerebral organoids, which include interneurons and oligodendrocytes (OLs). OLs are fundamental for brain development. Abundant studies have displayed that brain organoids can recapitulate fundamental and vital features of the human brain, such as cellular regulation and distribution, neuronal networks, electrical activities, and physiological structure. The organoids contain essential ventral brain domains and functional cortical interneurons, which are similar to the developing cortex and medial ganglionic eminence (MGE). So, brain organoids have provided a singular model to study and investigate neurological disorder mechanisms and therapeutics. Furthermore, the blood brain barrier (BBB) organoids modeling contributes to accelerate therapeutic discovery for the treatment of several neuropathologies. In this review, we summarized the advances of the brain organoids applications to investigate neurological disorder mechanisms such as neurodevelopmental and neurodegenerative disorders, mental disorders, brain cancer, and cerebral viral infections. We discussed brain organoids’ therapeutic application as a potential therapeutic unique method and highlighted in detail the challenges and hurdles of organoid models.
The Therapeutic Effects of Nigella sativa on Skin Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Nasiri Naser , Ilaghi Nezhad Mozhde , Sharififar Fariba , Khazaneha Mahdieh , Najafzadeh Mohammad Javad , Mohamadi Neda
Published: December 2022

The aim of this systematic review was to identify randomized controlled trials that looked at the effects of Nigella sativa in any form on different skin diseases. Up to March 2022, the online databases of Scopus, Web of Science, PubMed, Embase, Google Scholar, and Cochrane trials were searched. This study included 14 records of people who had experienced different types of skin disease including atopic dermatitis, vulgaris, arsenical keratosis, psoriasis, vitiligo, acute cutaneous leishmaniasis, warts, eczema, and acne. The mean SD age of the patients was 28.86 (4.49); [range: 18.3–51.4], with females accounting for 69% (506 out of 732) of the total. The follow-up mean SD was 8.16 (1.3) (ranged: 4 days to 24 weeks). The odds ratio (OR) was found to be 4.59 in a meta-analysis (95% CI: 2.02, 10.39). Whereas the null hypothesis in this systematic review was that lotion had no impact, OR 4.59 indicated that lotion could be effective. The efficacy of N. sativa essential oil and extract has been demonstrated in most clinical studies. However, more research is needed to completely evaluate and validate the efficacy or inadequacy of therapy with N. sativa, although it appears that it can be used as an alternative treatment to help people cope with skin problems.
Gut Microbiota Promotes Immune Tolerance by Regulating RORγt+ Treg Cells in Food Allergy
Authors: Ning Xixi , Lei Zengjie , Rui Binqi , Li Yuyuan , Li Ming
Published: December 2022

Food allergy is a significant public health problem troubling people, and the incidence has been on the rise in the past decade. Emerging evidence suggests an influence of the gut microbiota in susceptibility to food allergies. Epidemiological studies have shown an association between altered exposure to the microbiome and the risk of food allergies. Intervention of the gut microbiota in germ-free mice or supplementation of probiotics can regulate the proliferation of regulatory T (Treg) cells in mice and inhibit food allergy by promoting the expression of receptor-associated orphan γt+ (RORγt+) regulatory T (Treg) cells and inhibiting the proliferation of T helper 2 (Th2) and Th17 cells. This paper reviews the current research progress on how the gut microbiota enhances immune tolerance to prevent food allergy through RORγt+ Treg, hoping to provide some new ideas and effective targets for the prophylaxis of food allergy.
A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma
Authors: Lee Hyun-Sung , Jang Hee-Jin , Ramineni Maheshwari , Wang Daniel Y. , Ramos Daniela , Choi Jong Min , Splawn Taylor , Espinoza Monica , Almarez Michelle , Hosey Leandria , Jo Eunji , Hilsenbeck Susan , Amos Christopher I. , Ripley R. Taylor , Burt Bryan M.
Published: December 2022

Purpose:

We report the results of a phase II, randomized, window-of-opportunity trial of neoadjuvant durvalumab versus durvalumab plus tremelimumab followed by surgery in patients with resectable malignant pleural mesothelioma (MPM; NCT02592551).

Patients and Methods:

The primary objective was alteration of the intratumoral CD8/regulatory T cell (Treg) ratio after combination immune checkpoint blockade (ICB) therapy. Secondary and exploratory objectives included other changes in the tumor microenvironment, survival, safety, tumor pathologic response (PR), and systemic immune responses.

Results:

Nine patients received monotherapy and 11 received combination therapy. Seventeen of the 20 patients (85%) receiving ICB underwent planned thoracotomy. Both ICB regimens induced CD8 T-cell infiltration into MPM tumors but did not alter CD8/Treg ratios. At 34.1 months follow-up, patients receiving combination ICB had longer median overall survival (not reached) compared with those receiving monotherapy (14.0 months). Grade ≥3 immunotoxicity occurred in 8% of patients in the monotherapy group and 27% of patients in the combination group. Tumor PR occurred in 6 of 17 patients receiving ICB and thoracotomy (35.3%), among which major PR (>90% tumor regression) occurred in 2 (11.8%). Single-cell profiling of tumor, blood, and bone marrow revealed that combination ICB remodeled the immune contexture of MPM tumors; mobilized CD57+ effector memory T cells from the bone marrow to the circulation; and increased the formation of tertiary lymphoid structures in MPM tumors that were rich in CD57+ T cells.

Conclusions:

These data indicate that neoadjuvant durvalumab plus tremelimumab orchestrates de novo systemic immune responses that extend to the tumor microenvironment and correlate with favorable clinical outcomes.
A Novel Tumor-Promoting Role for Nuclear Factor IX in Glioblastoma Is Mediated through Transcriptional Activation of GINS1
Authors: Ge Ruixiang , Wang Chenci , Liu Jiangang , Jiang Haibo , Jiang Xiaochun , Liu Zhuohao
Published: December 2022

Our previous study illustrated that nuclear factor IX (NFIX) promotes glioblastoma (GBM) progression by inducing migration and proliferation of GBM cells. However, the underlying mechanism of how NFIX regulates GBM cell proliferation remains obscure. In this study, we uncovered that Go-Ichi-Ni-San 1 (GINS1) is upregulated and positively correlated with NFIX in human GBM specimen. NFIX silencing downregulates the expression of GINS1, which is pivotal for cell-cycle progression and proliferation of GBM cells. Replenishment of GINS1 largely rescues the NFIX-null effect on GBM cell proliferation. Mechanistic investigation revealed that NFIX transcriptionally actives GINS1 expression by directly binding to promoter region (-1779 to -1793bp) of the GINS1 gene. Furthermore, knockdown of NFIX sensitizes GBM cells to DNA damage-inducing agents including doxorubicin and temozolomide, in a GINS1-dependent manner.

Implications:

Our study highlights that targeting NFIX–GINS1 axis could be a novel and potential therapeutic approach for GBM treatment.
The Potential of Transcranial Alternating Current Stimulation to Alleviate Dual-Task Gait Costs in Older Adults: Insights from a Double-Blinded Pilot Study
Authors: Sayig-Keren Rony M. , Dagan Moria , Cornejo Thumm Pablo , Brozgol Marina , Gazit Eran , Manor Brad , Hausdorff Jeffrey M.
Published: December 2022

Background: The performance of an attention-demanding task while walking, i.e., dual-tasking, leads to dual-task costs (e.g., reduced gait speed) in older adults. Previous studies have shown that dual-task costs in gait are associated with future falls and cognitive decline. According to the communication through coherence hypothesis, transcranial alternating current stimulation (tACS) might help alleviate this problem. Objective: The aim of this study was to examine the effects of a single session of theta-tACS targeting the left fronto-parietal network (L-FPN) on dual-task walking and cognitive function compared to sham stimulation and transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex, a node within the L-FPN. Methods: Twenty older adults completed a four-visit, double-blinded, within-subject, cross-over study in which usual-walking, dual-task walking, and cognitive function were evaluated before and immediately after 20 min of tACS, tDCS, or sham (order randomized) stimulation. Dual-task costs to gait speed (primary outcome) and other measures were analyzed. Results: The dual-task cost to gait speed tended to be lower (i.e., better) after tACS (p = 0.067, Cohen’s d = 0.433∼small); tDCS significantly reduced this dual-task cost (p = 0.012, Cohen’s d = 0.618∼medium), and sham stimulation had no effect (p = 0.467). tACS significantly reduced the dual-task cost to step length (p = 0.037, Cohen’s d = 0.502∼medium); a trend was seen after tDCS (p = 0.069, Cohen’s d = 0.443∼small). No statistical differences were found for other measures of gait or cognitive function. Conclusions: The positive effects of tACS on dual-task gait speed and step length were roughly similar to those seen with tDCS. These results suggest that tACS affects the fronto-parietal network and, similar to tDCS, tACS may improve dual-tasking. Nonetheless, to achieve larger benefits and differentiate the effects of tACS and tDCS on brain function and dual-task walking in older adults, other stimulation montages and protocols should be tested.
The Duration of Neonatal Phototherapy and Allergic Disorders: The Japan Environment and Children’s Study
Authors: Hotta Masashi , Ueda Kimiko , Ikehara Satoyo , Tanigawa Kanami , Nakayama Hirofumi , Wada Kazuko , Kimura Tadashi , Ozono Keiichi , Sobue Tomotaka , Iso Hiroyasu ,   Japan Environment and Children’s Study Group
Published: December 2022

Introduction: Currently, the association between the duration of neonatal phototherapy and the risk of allergic disorders has not been reported. This observational cohort study aimed to examine the association between allergic disorders, including food allergies, that are present before 3 years of age and the duration of phototherapy using the nationwide birth cohort data. Methods: The Japan Environment and Children’s Study was a nationwide birth cohort study. Data of 77,064 infants aged 1 year, 1.5 years, 2 years, and 3 years were analyzed. We divided the participants into three groups: no phototherapy, short phototherapy (1–24 h), and long phototherapy (>24 h) and evaluated the cumulative incidence of allergic disorders before 3 years of age, including asthma, atopic dermatitis, and food allergies. Logistic regression analysis was performed to assess the impact of phototherapy duration on the cumulative incidence of allergic disorders. Results: After adjustment for potential risk factors, long phototherapy was found to be positively associated with food allergies at age 2 years (OR: 1.16; 95% CI: 1.01–1.33) and all allergic disorders at age 3 years (OR: 1.12; 95% CI: 1.01–1.24), including food allergies (OR 1.18; 95% CI: 1.04–1.35). Conclusion: A long duration of neonatal phototherapy was positively associated with the risk of allergic disorders, especially food allergies.