bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Pulse-Based Measurement Technique for Zinc–Air Battery Parameters
Authors: Hu Lin , Xu Xianzhi
Published: September 2023

Zinc–air batteries possess advantages such as high energy density, low operational costs, and abundant reserves of raw materials, demonstrating broad prospects for applications in areas like stationary power supplies and emergency power sources. However, despite significant advancements in zinc–air battery technology, a comprehensive measurement model for zinc–air battery parameters is still lacking. This paper utilizes a gas diffusion model to separately calculate the concentration polarization of zinc–air batteries, decoupling it from electrochemical polarization and ohmic polarization, simplifying the equivalent circuit model of zinc–air batteries into a first-order RC circuit. Subsequently, based on the simplified equivalent circuit model and gas diffusion model, a zinc–air battery parameter measurement technique utilizing current pulse methods is proposed, with predictions made for the dynamic voltage response during current pulse discharges. Validation of this method was conducted through single current pulses and step current pulses. Experimental results demonstrate the method’s capability to accurately measure zinc–air battery parameters and predict the dynamic voltage response.
The Blasting Vibration Characteristics of Layered Rock Mass under High-Pressure Gas Impact
Authors: Wei Haixia , Li Dongbing , Zhu Jie , Yang Xiaolin , Chu Huaibao
Published: September 2023

Firstly, the experimental test of blasting vibration was carried out to study the propagation characteristics of the peak particle velocity (PPV) and dominant frequency (DF) of the blasting vibration of layered rock mass under high-pressure gas impact. The test results show that the PPV and DF of blasting vibration of layered rock mass decrease gradually with the increase in distance from the explosion source. The PPV and DF of layered rock mass under the same impact pressure of high-pressure gas are lower than those of single rock mass at the same measuring points. With the increase in hole spacing, the PPV and DF of blasting vibration become smaller, and the blasting effect first becomes better and then worse. Next, the relationship models between the PPV and DF and their influencing factors were deduced by the dimensional analysis method, which can be simplified as exponential forms that decay with the scaled distance. In addition, through a numerical simulation test, it was found that the optimal hole spacing recommended in an excavation example of an underground pipe gallery is 100 cm. Finally, the blasting vibration effects under the two excavation methods of high-pressure gas impact and explosive blasting were numerically simulated and compared. The results indicate that high-pressure gas impact can significantly reduce the blasting vibration effect of layered rock mass compared with explosive blasting. This study has important theoretical guiding significance and practical value for revealing the propagation law, forecasting and controlling the harm of blasting vibration effect of layered rock mass caused by high-pressure gas impact.
Experimental Study on Combustion Behavior of U-Shaped Cables with Different Bending Forms and Angles
Authors: Chen Changkun , Du Wuhao , Xu Tong
Published: September 2023

Cables are usually bent into a U-shape to cross obstacles during installation: this includes the upward-bending mode (UBM) and the downward-bending mode (DBM). An experimental study was conducted to investigate the combustion behavior of U-shaped cables with the above bending forms and different angles. The ignition point was set in the middle of the U-shaped cables and the temperature distribution, flame spread rate (FSR), mass loss rate (MLR), flame dimensional characteristics, etc. were measured and analyzed. The results showed that FSR and MLR are positively related to the bending angles, and the FSR is the highest in UBM 90°, close to 6.51 cm/min, which is four times higher than that in the bending angle 0° condition. In the UBM, the heat radiation and convection from the cable flame to the unburned region were more intense and the “eruptive fire phenomenon” occurred during the combustion process, leading to a sharp increase in the FSR in a short time. However, the thermal convection and radiation from the burning region to the unburned region were weakened in the DBM. Meanwhile, the molten outer sheath (PE) would flow along the cables, heating and igniting the unburned region in the DBM. In addition, the FSR, MLR, and peak temperature increased in the UBM compared to the DBM. The highest flame temperature occurred in UBD 90°, approximately 1023 °C.
A Comparison of Three Protein Sources Used in Medium-Sized Litopenaeus vannamei: Effects on Growth, Immunity, Intestinal Digestive Enzyme Activity, and Microbiota Structure
Authors: Yuan Hang , Hu Naijie , Zheng Yudong , Hou Cuihong , Tan Beiping , Shi Lili , Zhang Shuang
Published: September 2023

The type of protein source in diets has many effects on shrimp. In this study, Litopenaeus vannamei with an initial body weight of 3.68 ± 0.002 g were fed for 8 weeks on three experimental diets (isoproteic: 41.00%; isolipidic: 7.61%) that were formulated using fish meal (FM), Chlorella sorokiniana (CHL), and Clostridium autoethanogenum protein (CAP) as the primary protein sources, respectively. This study examined the growth, non-specific immunity, intestinal digestion, and microbiota of L. vannamei after the feeding experiment concluded. Compared to the FM group, the findings indicate that the weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) of L. vannamei were notably enhanced via dietary CAP. The CHL group exhibited the highest levels of catalase (CAT), phenoloxidase (PO), and superoxide dismutase (SOD) activities in the gills of L. vannamei, whereas the FM group had the lowest levels. Conversely, the malondialdehyde (MDA) content showed the opposite trend. Both dietary CHL and CAP promoted the digestive enzyme activities of L. vannamei, with dietary CAP having a more pronounced promotional effect. An analysis of alpha diversity indicated that the consumption of dietary CHL substantially enhanced the abundance and diversity of microbiota in the intestinal tract of L. vannamei. Furthermore, the dietary CHL significantly increased the colonization of immune-associated beneficial bacteria and inhibited the colonization of pathogenic bacteria in the intestinal tract of L. vannamei, whereas dietary CAP mainly increased the colonization of growth-associated beneficial bacteria. Functional predictions showed that different dietary protein sources affect various metabolic activities and signaling pathways of L. vannamei, and some functions, including signal transduction, cell motility, and the immune system, were significantly enhanced in the CHL group. In summary, both dietary CHL and dietary CAP promoted growth and immunity in L. vannamei compared to dietary FM. The results of this study could be helpful for the sustainable development of shrimp farming.
Listeria monocytogenes Biofilms in Food-Associated Environments: A Persistent Enigma
Authors: Finn Lawrence , Onyeaka Helen , O’Neill Sally
Published: September 2023

Listeria monocytogenes (LM) is a bacterial pathogen responsible for listeriosis, a foodborne illness associated with high rates of mortality (20–30%) and hospitalisation. It is particularly dangerous among vulnerable groups, such as newborns, pregnant women and the elderly. The persistence of this organism in food-associated environments for months to years has been linked to several devastating listeriosis outbreaks. It may also result in significant costs to food businesses and economies. Currently, the mechanisms that facilitate LM persistence are poorly understood. Unravelling the enigma of what drives listerial persistence will be critical for developing more targeted control and prevention strategies. One prevailing hypothesis is that persistent strains exhibit stronger biofilm production on abiotic surfaces in food-associated environments. This review aims to (i) provide a comprehensive overview of the research on the relationship between listerial persistence and biofilm formation from phenotypic and whole-genome sequencing (WGS) studies; (ii) to highlight the ongoing challenges in determining the role biofilm development plays in persistence, if any; and (iii) to propose future research directions for overcoming these challenges.
Metagenomic Insights into the Microbiome and Resistance Genes of Traditional Fermented Foods in Arabia
Authors: Yasir Muhammad , Alkhaldy Areej A. , Soliman Samah Abdullah , Turkistani Safaa A. , Azhar Esam I.
Published: September 2023

This study uncovered microbial communities and evaluated the microbiological safety of traditional fermented foods consumed in the Arab region. Samples of dairy and non-dairy fermented foods—mish, jibneh, zabadi, and pickles—were collected from local markets in Saudi Arabia. Using the MiSeq system, samples were sequenced using 16S amplicons and shotgun metagenomics. Alpha and beta diversity indicated inter- and intra-variation in the studied fermented foods’ bacterial communities. In the case of mish, the replicates were clustered. Twenty-one genera were found to be significantly different (FDR < 0.05) in abundance in pairwise comparison of fermented foods. Five high-quality, metagenome-assembled genomes (MAGs) of Lactococcus lactis, Lactobacillus helveticus, Pseudoalteromonas nigrifaciens, Streptococcus thermophiles, and Lactobacillus acetotolerans were retrieved from the shotgun sequencing representing the dominant taxa in the studied fermented foods. Additionally, 33 genes that cause antimicrobial resistance (ARGs) against ten different antibiotic classes were detected. Metabolic pathways were abundant in the studied metagenomes, such as amino acid metabolism, carbohydrate metabolism, cofactors, and vitamin biosynthesis. Metagenomic evaluation of Arabian fermented foods, including the identification of probiotics, pathogenic bacteria, and ARGs, illustrates the importance of microbiological analysis in evaluating their health effects.
Development and Quality Characteristics of Elderly-Friendly Pulpo a La Gallega Prepared Using Texture-Modified Octopus (Octopus vulgaris) Arms
Authors: Kang Sang-In , Kim Jin-Soo , Park Sun-Young , Lee Seok-Min , Jang Mi-Soon , Oh Jae-Young , Choi Jae-Suk
Published: September 2023

Considering the need for developing new senior-friendly processed seafood, this study aimed to develop octopus pulpo with high preference and excellent quality characteristics for elderly individuals by optimizing the vinegar immersion and sous vide softening treatment conditions for octopus (Octopus vulgaris) arms. The optimal sous vide heating temperature (70.0–100.0 °C), time (69.5–170.5 min), and vinegar concentration (0.2–0.8%) were established using response surface methodology (RSM). The pulpo prototype was produced using an octopus arm softened under optimal conditions and seasoned with a potato and olive oil sauce. The physicochemical and nutritional properties of the prototype were evaluated, followed by sensory evaluation and safety assessments. The hardness of softened octopuses obtained by 0.48% vinegar immersion and sous vide treatment (84.3 °C, 139.8 min), determined using RSM, was 394.5 × 1000 N/m2, showing a reduction of 83.0%; this was confirmed by electron microscopic observation. The texture of the pulpo prototype with softened octopus arms showed the highest preference (8.4 points) and high physicochemical and nutritional properties. Overall, the octopus pulpo a La Gallega prototype produced using texture-modified octopus arms was suitable for consumption by elderly people with chewing disorders and could help improve their quality of life.
On the Molecular Selection of Exopolysaccharide-Producing Lactic Acid Bacteria from Indigenous Fermented Plant-Based Foods and Further Fine Chemical Characterization
Authors: Angelov Angel , Georgieva Aneliya , Petkova Mariana , Bartkiene Elena , Rocha João Miguel , Ognyanov Manol , Gotcheva Velitchka
Published: September 2023

Exopolysaccharides (EPSs) produced by lactic acid bacteria present a particular interest for the food industry since they can be incorporated in foods via in situ production by selected starter cultures or applied as natural additives to improve the quality of various food products. In the present study, 43 strains were isolated from different plant-based fermented foods and identified by molecular methods. The species found were distinctively specific according to the food source. Only six Lactiplantibacillus plantarum strains, all isolated from sauerkraut, showed the ability to produce exopolysaccharide (EPS). The utilization of glucose, fructose and sucrose was explored with regard to EPS and biomass accumulation by the tested strains. Sucrose was clearly the best carbon source for EPS production by most of the strains, yielding up to 211.53 mg/L by strain Lactiplantibacillus plantarum ZE2, while biomass accumulation reached the highest levels in the glucose-based culture medium. Most strains produced similar levels of EPS with glucose and fructose, while fructose was utilized more poorly for biomass production, yielding about 50% of biomass compared to glucose for most strains. Composition analysis of the EPSs produced by strain Lactiplantibacillus plantarum ZE2 from glucose (EPS-1) and fructose (EPS-2) revealed that glucose (80–83 mol%) and protein (41% w/w) predominated in both analyzed EPSs. However, the yield of EPS-1 was twice higher than that of EPS-2, and differences in the levels of all detected sugars were found, which shows that even for the same strain, EPS yield and composition vary depending on the carbon source. These results may be the basis for the development of tailored EPS-producing starter cultures for food fermentations, as well as technologies for the production of EPS for various applications.
Resonant Effects of a Bar on the Galactic Disk Kinematics Perpendicular to Its Plane
Authors: Korchagin Vladimir , Lutsenko Artem , Tkachenko Roman , Carraro Giovanni , Vieira Katherine
Published: September 2023

Detailed analysis of kinematics of the Milky Way disk in the solar neighborhood based on the GAIA DR3 catalog reveals the existence of peculiarities in the stellar velocity distribution perpendicular to the galactic plane. We study the influence of resonances—the outer Lindblad resonance and the outer vertical Lindblad resonance—of a rotating bar with stellar oscillations perpendicular to the plane of the disk, and their role in shaping the spatial and the velocity distributions of stars. We find that the Z and VZ distributions of stars with respect to LZ are affected by the outer Lindblad resonance. The existence of bar resonance with stellar oscillations perpendicular to the plane of the disk is demonstrated for a long (large semi-axis 5 kpc) and fast rotating bar with Ωb=60.0kms−1kpc−1. We show also that, in the model with the long and fast rotating bar, some stars in the 2:1 OLR region deviate far from their original places, entering the bar region. A combination of resonance excitation of stellar motions at the 2:1 OLR region together with strong interaction of the stars with the bar potential leads to the formation of the group of ‘escapees’, i.e., stars that deviate in R and Z—directions at large distances from the resonance region. Simulations, however, do not demonstrate any noticeable effect on VZ-distribution of stars in the solar neighborhood.
Orange Dye and Silicone Glue Composite Gel-Based Optimized Impedimetric and Capacitive Surface-Type Proximity Sensors
Authors: Karimov Khasan S. , Chani Muhammad Tariq Saeed , Fatima Noshin , Asiri Abdullah M. , Rahman Mohammed M.
Published: September 2023

Optimized surface-type impedimetric and capacitive proximity sensors have been fabricated on paper substrates by using rubbing-in technology. The orange dye (OD) and silicone glue (SG) composite-gel films were deposited on the zig-zag gap between two aluminum electrodes fixed on a paper (dielectric) substrate. The effect of proximity of various objects (receivers) on the impedance and the capacitance of the sensors was investigated. These objects were semi-cylindrical aluminum (metallic) foil, a cylindrical plastic tube filled with water, a kopeck-shaped plastic tube filled with carbon nanotubes and a human finger. The mechanism of sensing was based on the change in impedance and/or the capacitance of the sensors with variation of proximity between the surfaces of the sensor and the object. On decreasing proximity, the impedance of the sensors increased while the capacitance decreased. The impedimetric proximity sensitivities of CNT, water, metal-based receivers and the finger were up to 60 × 103 Ω/mm, 35 × 103 Ω/mm, 44 × 103 Ω/mm and 6.2 × 103 Ω/mm, respectively, while their capacitive sensitivities were −19.0 × 10−2 pF/mm, −16.0 × 10−2 pF/mm, −16.4 × 10−2 pF/mm and −1.8 × 10−2 pF/mm. If needed for practical application, the sensors can be built in to the Wheatstone bridge, which can also increase the sensitivity of the measurement. Moreover, the sensor’s materials are low cost, while the fabrication technique is easy and ecologically friendly. The sensor can also be used for demonstrative purposes in school and college laboratories.
Physicochemical Response of External Plant Growth Regulator in the Cutting Process of Mulberry
Authors: Sun Jiajia , Dou Hao , Chen Hanlei , Wang Yilin , Wang Tiantian , Quan Jin’e , Bi Huitao
Published: September 2023

Adventitious roots play a crucial role in the nourishment and propagation of arboreal vegetation. In order to shed light on the physiological and biochemical characteristics of the challenging-to-propagate mulberry tree species, an investigation was conducted. This study aimed to compare the responses of various root morphological indicators, endogenous hormones, and oxidase activities in the “Yueshenda 10” fruit mulberry, at different stages of treatment. The ultimate objective was to identify the factors influencing the process of root development. The findings revealed a distinct ”/\“ pattern in the levels of IAA and JA within the cuttings. Conversely, the changes in ABA, ZR, and GA3 exhibited a ”/\/“ pattern. The fluctuation of the IAA/ABA values followed a ”\/\“ mode, whereas the IAA/ZR values initially increased, followed by a subsequent decrease. The correlation between the initial concentrations of these five endogenous hormones and the rooting rate displayed variations. Notably, IAA demonstrated the strongest association with the rooting rate, exhibiting a positive correlation with both IAA and ZR. Regarding the activity of three antioxidant enzymes (IAAO, POD, and PPO), a ”/\“ trend was observed, wherein the enzyme activity increased under ABT1 treatment. However, the peak activity levels of the enzymes appeared during different periods: callus generation, rooting induction, and adventitious root expression, respectively. Overall, the most effective treatment for promoting root development and significantly enhancing the root growth parameters of mulberry was found to be 800 mg/L ABT1. Exogenous hormone treatment expedited the synthesis of antioxidant enzymes, thereby shortening the rooting time and facilitating root formation.
Sustainable Smart Cities—Social Media Platforms and Their Role in Community Neighborhood Resilience—A Systematic Review
Authors: Balakrishnan Soumya , Elayan Suzanne , Sykora Martin , Solter Marin , Feick Rob , Hewitt Christopher , Liu Yi Qiao , Shankardass Ketan
Published: September 2023

The COVID-19 pandemic took most communities off guard and has highlighted gaps in community preparedness and resilience in spite of the numerous technological advancements and the variety of available social media platforms that many relied on during lockdown periods. This served to emphasise the necessity for exploring the roles of social media and smart city technologies in mitigating pandemic impacts. In this systematic literature review, we examined twelve articles on social media usage and smart city technologies and their contributions to community resilience during COVID-19. The analysis focused on the use of social media platforms and smart city technologies during and after lockdown periods, examining their role in fostering community resilience. Results indicate that social media and smart city technologies were instrumental in helping communities adapt and recover from the pandemic. While past studies have examined community resilience, social media, or smart cities separately, there is limited literature collating insights on the three elements combined. We therefore argue that these technologies, employed collaboratively, enhance community resilience during crises. Nevertheless, further research is recommended, particularly on urban resilience and comparative analyses to deepen our understanding of the complex interplay between these variables.
Nonlinear Hierarchical Effects of Housing Prices and Built Environment Based on Multiscale Life Circle—A Case Study of Chengdu
Authors: Song Yandi , Zhang Shaoyao , Deng Wei
Published: September 2023

Determining the optimal planning scale for urban life circles and analyzing the associated built environment factors are crucial for comprehending and regulating residential differentiation. This study aims to bridge the current research void concerning the nonlinear hierarchical relationships between the built environment and residential differentiation under the multiscale effect. Specifically, six indicators were derived from urban crowdsourcing data: diversity of built environment function (DBEF1), density of built environment function (DBEF2), blue–green environment (BGE), traffic accessibility (TA), population vitality (PV), and shopping vitality (SV). Then, a gradient boosting decision tree (GBDT) was applied to derive the analysis of these indicators. Finally, the interpretability of machine learning was leveraged to quantify the relative importance and nonlinear relationships between built environment indicators and housing prices. The results indicate a hierarchical structure and inflection point effect of the built environment on residential premiums. Notably, the impact trend of the built environment on housing prices within a 15 min life circle remains stable. The effect of crowd behavior, as depicted by PV and SV, on housing prices emerges as the most significant factor. Furthermore, this study also categorizes housing into common and high-end residences, thereby unveiling that distinct residential neighborhoods exhibit varying degrees of dependence on the built environment. The built environment exerts a scale effect on the formation of residential differentiation, with housing prices exhibiting increased sensitivity to the built environment at a smaller life circle scale. Conversely, the effect of the built environment on housing prices is amplified at a larger life circle scale. Under the dual influence of the scale and hierarchical effect, this framework can dynamically adapt to the uncertainty of changes in life circle planning policies and residential markets. This provides strong theoretical support for exploring the optimal life circle scale, alleviating residential differentiation, and promoting group fairness.
Efficacy of Lenvatinib Combined with Transcatheter Intra-Arterial Therapies for Patients with Advanced-Stage of Hepatocellular Carcinoma: A Propensity Score Matching
Authors: Shimose Shigeo , Iwamoto Hideki , Niizeki Takashi , Tanaka Masatoshi , Shirono Tomotake , Moriyama Etsuko , Noda Yu , Nakano Masahito , Suga Hideya , Kuromatsu Ryoko , Torimura Takuji , Koga Hironori , Kawaguchi Takumi
Published: September 2023

This study aimed to evaluate the effect of lenvatinib (LEN) combined with transcatheter intra-arterial therapy (TIT) for advanced-stage hepatocellular carcinoma (HCC) after propensity score matching (PSM). This retrospective study enrolled 115 patients with advanced-stage HCC who received LEN treatment. The patients were categorized into the LEN combined with TIT group (n = 30) or the LEN monotherapy group (n = 85). After PSM, 38 patients (LEN + TIT group, n = 19; LEN monotherapy group, n = 19) were analyzed. The median overall survival (OS) in the LEN + TIT group was significantly higher than that in the LEN monotherapy group (median survival time (MST): 28.1 months vs. 11.6 months, p = 0.014). The OS in the LEN combined with transcatheter arterial chemoembolization and LEN combined with hepatic arterial infusion chemotherapy groups was significantly higher than that in the LEN monotherapy group (MST 20.0 vs. 11.6 months, 30.2 vs. 11.6 months, p = 0.048, and p = 0.029, respectively). Independent factors associated with OS were alpha-fetoprotein and LEN combined with TIT. The indications for LEN combined with TIT were age <75 years and modified albumin bilirubin (m-ALBI) grade 1. We concluded that LEN combined with TIT may improve prognosis compared with LEN monotherapy in patients with advanced-stage HCC.
Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma
Authors: Keuthan Casey J. , Schaub Julie A. , Wei Meihan , Fang Weixiang , Quillen Sarah , Kimball Elizabeth , Johnson Thomas V. , Ji Hongkai , Zack Donald J. , Quigley Harry A.
Published: September 2023

A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.
Examining the Transcriptomic and Biochemical Signatures of Bacillus subtilis Strains: Impacts on Plant Growth and Abiotic Stress Tolerance
Authors: Chang Peter E. , Wu Yun-Hsiang , Tai Ciao-Yun , Lin I-Hung , Wang Wen-Der , Tseng Tong-Seung , Chuang Huey-wen
Published: September 2023

Rhizobacteria from various ecological niches display variations in physiological characteristics. This study investigates the transcriptome profiling of two Bacillus subtilis strains, BsCP1 and BsPG1, each isolated from distinct environments. Gene expression linked to the synthesis of seven types of antibiotic compounds was detected in both BsCP1 and BsPG1 cultures. Among these, the genes associated with plipastatin synthesis were predominantly expressed in both bacterial strains. However, genes responsible for the synthesis of polyketide, subtilosin, and surfactin showed distinct transcriptional patterns. Additionally, genes involved in producing exopolysaccharides (EPS) showed higher expression levels in BsPG1 than in BsCP1. Consistently with this, a greater quantity of EPS was found in the BsPG1 culture compared to BsCP1. Both bacterial strains exhibited similar effects on Arabidopsis seedlings, promoting root branching and increasing seedling fresh weight. However, BsPG1 was a more potent enhancer of drought, heat, and copper stress tolerance than BsCP1. Treatment with BsPG1 had a greater impact on improving survival rates, increasing starch accumulation, and stabilizing chlorophyll content during the post-stress stage. qPCR analysis was used to measure transcriptional changes in Arabidopsis seedlings in response to BsCP1 and BsPG1 treatment. The results show that both bacterial strains had a similar impact on the expression of genes involved in the salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Likewise, genes associated with stress response, root development, and disease resistance showed comparable responses to both bacterial strains. However, treatment with BsCP1 and BsPG1 induced distinct activation of genes associated with the ABA signaling pathway. The results of this study demonstrate that bacterial strains from different ecological environments have varying abilities to produce beneficial metabolites for plant growth. Apart from the SA and JA signaling pathways, ABA signaling triggered by PGPR bacterial strains could play a crucial role in building an effective resistance to various abiotic stresses in the plants they colonize.
Neurodegenerative Diseases: Molecular Mechanisms and Therapies
Authors: Zhou Zhi Dong , Kihara Alexandre Hiroaki
Published: September 2023

Neurodegenerative diseases are characterized by the progressive degeneration or death of neurons in the central or peripheral nervous system [...]
Antimicrobial Activity and Toxicity of Newly Synthesized 4-[4-(benzylamino)butoxy]-9H-carbazole Derivatives
Authors: Niedziałkowska Katarzyna , Felczak Aleksandra , Głowacka Iwona E. , Piotrowska Dorota G. , Lisowska Katarzyna
Published: September 2023

One of the main challenges of medicinal chemistry is the search for new substances with antimicrobial potential that could be used in the fight against pathogenic microorganisms. Therefore, the antimicrobial activity of newly synthesized compounds is still being investigated. Carbazole-containing compounds appear to be promising antibacterial, antifungal, and antiviral agents. The aim of this study was to examine the antimicrobial potential and toxicity of newly synthesized isomeric fluorinated 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives. Their antimicrobial activity against bacteria and fungi was tested according to CLSI guidelines. Similarly to previously studied carbazole-containing compounds, the tested derivatives showed the ability to effectively inhibit the growth of Gram-positive bacteria. The addition of carbazole derivatives 2, 4, and 8 at the concentration of 16 µg/mL caused the inhibition of S. aureus growth by over 60%. The MIC value of compounds 2–5 and 7–10 was 32 µg/mL for Staphylococcus strains. Gram-negative strains of E. coli and P. aeruginosa were found to be more resistant to the tested carbazole derivatives. E. coli cells treated with compounds 3 and 8 at a concentration of 64 µg/mL resulted in a greater-than-40% reduction in bacterial growth. In the case of the P. aeruginosa strain, all compounds in the highest concentration that we tested limited growth by 35–42%. Moreover, an over-60% inhibition of fungal growth was observed in the cultures of C. albicans and A. flavus incubated with 64 µg/mL of compounds 2 or 7 and 1 or 4, respectively. The hemolysis of red blood cells after their incubation with the tested carbazole derivatives was in the range of 2–13%. In the case of human fibroblast cells, the toxicity of the tested compounds was higher. Derivative 1, functionalized with fluorine in position 2 and its hydrobromide, was the least toxic. The obtained results indicated the antimicrobial potential of the tested 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives, especially against S. aureus strains; therefore, it is worth further modifying these structures, in order to enhance their activity against pathogenic microorganisms.
Antibody–Drug Conjugates in Breast Cancer: Current Status and Future Directions
Authors: Mark Cynthia , Lee Jin Sun , Cui Xiaojiang , Yuan Yuan
Published: September 2023

Antibody drug conjugates (ADCs) are novel medications that combine monoclonal antibodies with cytotoxic payloads, enabling the selective delivery of potent drugs to cancer cells expressing specific surface antigens. This targeted strategy seeks to optimize treatment effectiveness while reducing the risk of systemic toxicity, distinguishing ADCs from conventional chemotherapy. The rapid growth in ADC research has led to numerous developments and approvals for cancer treatment, with significant impacts on the management of breast cancer. ADCs like T-DXd for HER2-low disease and sacituzumab govitecan for triple negative breast cancer (TNBC) have provided valuable options for challenging subtypes of breast cancer. However, essential questions still need to be addressed, including the optimal order of ADCs amidst the growing number of newly developed ones and strategies to overcome resistance mechanisms. Preclinical studies have shed light on potential resistance mechanisms, emphasizing the potential benefit of combinational approaches with other agents such as immune checkpoint inhibitors (ICIs) and targeted tyrosine kinase inhibitors (TKIs) to enhance treatment effectiveness. Additionally, personalized approaches based on molecular profiling hold promise in tailoring ADC treatments to individual tumors, identifying unique molecular markers for each patient to optimize treatment efficacy while minimizing side effects.
What about Current Diversity of Mycolactone-Producing Mycobacteria? Implication for the Diagnosis and Treatment of Buruli Ulcer
Authors: Combe Marine , Cherif Emira , Blaizot Romain , Breugnot Damien , Gozlan Rodolphe Elie
Published: September 2023

The identification of an emerging pathogen in humans can remain difficult by conventional methods such as enrichment culture assays that remain highly selective, require appropriate medium and cannot avoid misidentifications, or serological tests that use surrogate antigens and are often hampered by the level of detectable antibodies. Although not originally designed for this purpose, the implementation of polymerase-chain-reaction (PCR) has resulted in an increasing number of diagnostic tests for many diseases. However, the design of specific molecular assays relies on the availability and reliability of published genetic sequences for the target pathogens as well as enough knowledge on the genetic diversity of species and/or variants giving rise to the same disease symptoms. Usually designed for clinical isolates, molecular tests are often not suitable for environmental samples in which the target DNA is mixed with a mixture of environmental DNA. A key challenge of such molecular assays is thus to ensure high specificity of the target genetic markers when focusing on clinical and environmental samples in order to follow the dynamics of disease transmission and emergence in humans. Here we focus on the Buruli ulcer (BU), a human necrotizing skin disease mainly affecting tropical and subtropical areas, commonly admitted to be caused by Mycobacterium ulcerans worldwide although other mycolactone-producing mycobacteria and even mycobacterium species were found associated with BU or BU-like cases. By revisiting the literature, we show that many studies have used non-specific molecular markers (IS2404, IS2606, KR-B) to identify M. ulcerans from clinical and environmental samples and propose that all mycolactone-producing mycobacteria should be definitively considered as variants from the same group rather than different species. Importantly, we provide evidence that the diversity of mycolactone-producing mycobacteria variants as well as mycobacterium species potentially involved in BU or BU-like skin ulcerations might have been underestimated. We also suggest that the specific variants/species involved in each BU or BU-like case should be carefully identified during the diagnosis phase, either via the key to genetic identification proposed here or by broader metabarcoding approaches, in order to guide the medical community in the choice for the most appropriate antibiotic therapy.
Loss of MXRA8 Delays Mammary Tumor Development and Impairs Metastasis
Authors: Simpson Kaitlyn E. , Staikos Christina A. , Watson Katrina L. , Moorehead Roger A.
Published: September 2023

Matrix-remodeling-associated protein 8 or MXRA8 is a transmembrane protein that can bind arthritogenic alpha viruses like the Chikungunya virus and provide viral entry into cells. MXRA8 can also interact with integrin β3 and thus possibly regulate cell–cell interactions and binding to the extracellular matrix. While MXRA8 has been associated with reduced survival in patients with colorectal and renal clear cell cancers, the role of MXRA8 in breast cancer remains largely unexplored. Therefore, the aim of this research was to determine the role of MXRA8 in breast cancer by knocking out MXRA8 in the human triple-negative breast cancer cell line MDA-MB-231. The loss of MXRA8 reduced cell proliferation in vitro but had no effect on apoptosis or migration in cultured cells. However, the loss of MXRA8 significantly delayed tumor development and reduced metastatic dissemination to the lungs in a xenograft model. RNA sequencing identified three genes, ADMATS1, TIE1, and BMP2, whose expression were significantly reduced in MXRA8-knockout tumors compared to control tumors. MXRA8 staining of a human breast cancer tissue array revealed higher levels of MXRA8 in primary tumors and metastases of aggressive tumor subtypes (TNBC and HER2+) compared to less aggressive, ER+ breast cancers. Our findings demonstrate for the first time that MXRA8 regulates the progression of human TNBC possibly through influencing the interaction of tumor cells with their microenvironment.
Metabolomic Approach Based on Analytical Techniques for the Detection of Secondary Metabolites from Humulus lupulus L. Dried Leaves
Authors: Taiti Cosimo , Di Matteo Giacomo , Spano Mattia , Vinciguerra Vittorio , Masi Elisa , Mannina Luisa , Garzoli Stefania
Published: September 2023

Currently, the leaves of the hop plant (Humulus lupulus L.) are an unexploited and still little-investigated agricultural by-product. In our study, with the aim of exploring the metabolome of dried hop leaves (Chinook cultivar), a metabolomic approach was applied using multiple analytical tools such as SPME/GC–MS, GC–MS, PTR-ToF-MS, and NMR to identify the secondary metabolites. The obtained results showed the presence of a high number of components belonging to different chemical classes. In fact, thanks to the multi-methodological approach, volatile organic compounds (VOCs) with low molecular weight, terpenic compounds, fatty acids, sugars, amino acids, organic acids, and alcohols have been detected and identified. Among the revealed terpenes in the untreated matrix, the sesquiterpenes α-humulene, β-caryophyllene, and α-copaene were the most abundant. Among the saturated and unsaturated fatty acids, palmitic and linolenic acids, respectively, were those with the highest relative percentages. Particularly relevant was the sugar content, where sucrose was the main exponent while glutamate and asparagine were the principal detected amino acids. Conversely, alcohols and organic acids were the least abundant compound classes, and xanthohumol was also identified in the methanolic extract.
GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer
Authors: Elahi Najafi Mohammad Amin , Yasui Masato , Teramoto Yuki , Tatenuma Tomoyuki , Jiang Guiyang , Miyamoto Hiroshi
Published: September 2023

The precise molecular mechanisms responsible for resistance to cisplatin-based chemotherapy in patients with bladder cancer remain elusive, while we have indicated that androgen receptor (AR) activity in urothelial cancer is associated with its sensitivity. Our DNA microarray analysis in control vs. AR-knockdown bladder cancer sublines suggested that the expression of a GABA B receptor GABBR2 and AR was correlated. The present study aimed to determine the functional role of GABBR2 in modulating cisplatin sensitivity in bladder cancer. AR knockdown and dihydrotestosterone treatment considerably reduced and induced, respectively, GABBR2 expression, and the effect of dihydrotestosterone was at least partially restored by an antiandrogen hydroxyflutamide. A chromatin immunoprecipitation assay further revealed the binding of AR to the promoter region of GABBR2 in bladder cancer cells. Meanwhile, GABBR2 expression was significantly elevated in a cisplatin-resistant bladder cancer subline, compared with control cells. In AR-positive bladder cancer cells, knockdown of GABBR2 or treatment with a selective GABA B receptor antagonist, CGP46381, considerably enhanced the cytotoxic activity of cisplatin. However, no additional effect of CGP46381 on cisplatin-induced growth suppression was seen in GABBR2-knockdown cells. Moreover, in the absence of cisplatin, CGP46381 treatment and GABBR2 knockdown showed no significant changes in cell proliferation or migration. These findings suggest that GABBR2 represents a key downstream effector of AR signaling in inducing resistance to cisplatin treatment. Accordingly, inhibition of GABBR2 has the potential of being a means of chemosensitization, especially in patients with AR/GABBR2-positive bladder cancer.
Exploring the Anti-Hypoxaemia Effect of Hydromethylthionine: A Prospective Study of Phase 3 Clinical Trial Participants
Authors: Arastoo Mohammad , Mazanetz Michael P. , Miller Sonya , Shiells Helen , Hull Claire , Robinson Keith , Storey John M. D. , Harrington Charles R. , Wischik Claude M.
Published: September 2023

Methylthioninium chloride (MTC) is a standard treatment for methaemoglobinaemia. A preparation of reduced MTC has been reported to increase blood oxygen saturation (SpO2) and lower respiratory rates in patients with severe COVID-19. We have developed a stable form of reduced methylthionine (hydromethylthionine-mesylate, HMTM) having a benign safety profile in two Phase 3 trials in Alzheimer’s disease. The aim of this prospective study was to determine the effects of oral HMTM on SpO2 and methaemoglobin (metHb) levels in a cohort of patients with mild hypoxaemia not due to COVID-19. Eighteen participants randomised to a single dose of 4, 75, 100 or 125 mg doses of HMTM had SpO2 levels below 94% at baseline. Patients were routinely monitored by pulse oximetry after 4 h, and after 2 and 6 weeks of twice daily dosing. Significant ~3% increases in SpO2 occurred within 4 h and were sustained over 2 and 6 weeks with no dose differences. There were small dose-dependent increases (0.060–0.162%) in metHb levels over 2 to 6 weeks. Minimum-energy computational chemistry revealed that HMT can bind within 2.10 Å of heme iron by donating a pair of electrons from the central nitrogen of HMT to d orbitals of heme iron, but with lower affinity than oxygen. In conclusion, HMTM can increase SpO2 without reducing metHb by acting as a strong displaceable field ligand for heme iron. We hypothesise that this facilitates a transition from the low oxygen affinity T-state of heme to the higher affinity R-state. HMTM has potential as an adjunctive treatment for hypoxaemia.
Method Development for Determination of Doripenem in Human Plasma via Capillary Electrophoresis Coupled with Field-Enhanced Sample Stacking and Sweeping
Authors: Liang Hsin-Hua , Lin Yu-Chao , Hung Chin-Chuan , Hou Yu-Chi , Lin Yi-Hui
Published: September 2023

In this study, we established a novel capillary electrophoresis method for monitoring the concentration of doripenem in human plasma. As a time-dependent antibiotic, doripenem maximizes its antibacterial effects and minimizes the potential for antibiotic resistance through careful therapeutic drug monitoring. Two online preconcentration techniques, field-enhanced sample stacking (FESS) and sweeping, were coupled to enhance the detection sensitivity. Briefly, an uncoated fused silica capillary (40 cm × 50 μm i.d) was rinsed with a high conductivity buffer (HCB) composed of 150 mM phosphate buffer (NaH2PO4, pH 2.5) and 20% methanol. A large sample plug prepared in a low-conductivity phosphate buffer (50 mM NaH2PO4, pH 2.5) was then hydrodynamically injected (5 psi, 80 s) into the capillary. Under an applied voltage of −30 kV, the analyte was accumulated at the FESS boundary and swept by the negatively charged micelles toward the UV detector. Plasma samples were pretreated by solid-phase extraction (SPE) to eliminate endogenous interferences. The validation results demonstrated a high coefficient of determination (r2 > 0.9995) for the regression curve with impressive precision and accuracy: relative standard deviation (RSD) <5.86% and relative error <4.63%. The limit of detection (LOD, S/N = 3) for doripenem was determined to be 0.4 μg/mL. Compared to the conventional micellar electrokinetic chromatography method, our developed method achieved a sensitivity enhancement of up to 488-fold for doripenem. Furthermore, the newly developed method successfully quantified doripenem concentrations in plasma samples obtained from patients accepting doripenem regimens, proving its application potential in the clinical realm.
Development of a Macrophage-Related Risk Model for Metastatic Melanoma
Authors: Li Zhaoxiang , Zhang Xinyuan , Jin Quanxin , Zhang Qi , Yue Qi , Fujimoto Manabu , Jin Guihua
Published: September 2023

As a metastasis-prone malignancy, the metastatic form and location of melanoma seriously affect its prognosis. Although effective surgical methods and targeted drugs are available to enable the treatment of carcinoma in situ, for metastatic tumors, the diagnosis, prognosis assessment and development of immunotherapy are still pending. This study aims to integrate multiple bioinformatics approaches to identify immune-related molecular targets viable for the treatment and prognostic assessment of metastatic melanoma, thus providing new strategies for its use as an immunotherapy. Immunoinfiltration analysis revealed that M1-type macrophages have significant infiltration differences in melanoma development and metastasis. In total, 349 genes differentially expressed in M1-type macrophages and M2-type macrophages were extracted from the MSigDB database. Then we derived an intersection of these genes and 1111 melanoma metastasis-related genes from the GEO database, and 31 intersected genes identified as melanoma macrophage immunomarkers (MMIMs) were obtained. Based on MMIMs, a risk model was constructed using the Lasso algorithm and regression analysis, which contained 10 genes (NMI, SNTB2, SLC1A4, PDE4B, CLEC2B, IFI27, COL1A2, MAF, LAMP3 and CCDC69). Patients with high+ risk scores calculated via the model have low levels of infiltration by CD8+ T cells and macrophages, which implies a poor prognosis for patients with metastatic cancer. DCA decision and nomogram curves verify the high sensitivity and specificity of this model for metastatic cancer patients. In addition, 28 miRNAs, 90 transcription factors and 29 potential drugs were predicted by targeting the 10 MMIMs derived from this model. Overall, we developed and validated immune-related prognostic models, which accurately reflected the prognostic and immune infiltration characteristics of patients with melanoma metastasis. The 10 MMIMs may also be prospective targets for immunotherapy.