bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering
Authors: You Jiaqian , Liu Manxuan , Li Minghui , Zhai Shaobo , Quni Sezhen , Zhang Lu , Liu Xiuyu , Jia Kewen , Zhang Yidi , Zhou Yanmin
Published: April 2023

The process of repairing significant bone defects requires the recruitment of a considerable number of cells for osteogenesis-related activities, which implies the consumption of a substantial amount of oxygen and nutrients. Therefore, the limited supply of nutrients and oxygen at the defect site is a vital constraint that affects the regenerative effect, which is closely related to the degree of a well-established vascular network. Hypoxia-inducible factor (HIF-1α), which is an essential transcription factor activated in hypoxic environments, plays a vital role in vascular network construction. HIF-1α, which plays a central role in regulating cartilage and bone formation, induces vascular invasion and differentiation of osteoprogenitor cells to promote and maintain extracellular matrix production by mediating the adaptive response of cells to changes in oxygen levels. However, the application of HIF-1α in bone tissue engineering is still controversial. As such, clarifying the function of HIF-1α in regulating the bone regeneration process is one of the urgent issues that need to be addressed. This review provides insight into the mechanisms of HIF-1α action in bone regeneration and related recent advances. It also describes current strategies for applying hypoxia induction and hypoxia mimicry in bone tissue engineering, providing theoretical support for the use of HIF-1α in establishing a novel and feasible bone repair strategy in clinical settings.
Biotransformation of Natural Products and Phytochemicals: Metabolites, Their Preparation, and Properties
Authors: Valentová Kateřina
Published: April 2023

The term “biotransformation” refers to the process by which various compounds are biocatalyzed and enzymatically modified, as well as the metabolic changes that occur in organisms as a result of exposure to xenobiotics [...]
Advances in Antibody Design and Antigenic Peptide Targeting 2.0
Authors: Trier Nicole Hartwig , Houen Gunnar
Published: April 2023

Antibodies possess numerous important functions in diagnostics, both as therapeutics and as research tools [...]
Vitamin D Modulates the Response of Patient-Derived Metastatic Melanoma Cells to Anticancer Drugs
Authors: Piotrowska Anna , Zaucha Renata , Król Oliwia , Żmijewski Michał Aleksander
Published: April 2023

Melanoma is considered a lethal and treatment-resistant skin cancer with a high risk of recurrence, making it a major clinical challenge. Our earlier studies documented that 1,25(OH)2D3 and its low-calcaemic analogues potentiate the effectiveness of dacarbazine and cediranib, a pan-VEGFR inhibitor. In the current study, a set of patient-derived melanoma cultures was established and characterised as a preclinical model of human melanoma. Thus, patient-derived cells were preconditioned with 1,25(OH)2D3 and treated with cediranib or vemurafenib, a BRAF inhibitor, depending on the BRAF mutation status of the patients enrolled in the study. 1,25(OH)2D3 preconditioning exacerbated the inhibition of patient-derived melanoma cell growth and motility in comparison to monotherapy with cediranib. A significant decrease in mitochondrial respiration parameters, such as non-mitochondrial oxygen consumption, basal respiration and ATP-linked respiration, was observed. It seems that 1,25(OH)2D3 preconditioning enhanced cediranib efficacy via the modulation of mitochondrial bioenergetics. Additionally, 1,25(OH)2D3 also decreased the viability and mobility of the BRAF+ patient-derived cells treated with vemurafenib. Interestingly, regardless of the strict selection, cancer-derived fibroblasts (CAFs) became the major fraction of cultured cells over time, suggesting that melanoma growth is dependent on CAFs. In conclusion, the results of our study strongly emphasise that the active form of vitamin D, 1,25(OH)2D3, might be considered as an adjuvant agent in the treatment of malignant melanoma.
A Multi-Key with Partially Homomorphic Encryption Scheme for Low-End Devices Ensuring Data Integrity
Authors: Medileh Saci , Laouid Abdelkader , Hammoudeh Mohammad , Kara Mostefa , Bejaoui Tarek , Eleyan Amna , Al-Khalidi Mohammed
Published: April 2023

In today’s hyperconnected world, the Internet of Things and Cloud Computing complement each other in several areas. Cloud Computing provides IoT systems with an efficient and flexible environment that supports application requirements such as real-time control/monitoring, scalability, fault tolerance, and numerous security services. Hardware and software limitations of IoT devices can be mitigated using the massive on-demand cloud resources. However, IoT cloud-based solutions pose some security and privacy concerns, specifically when an untrusted cloud is used. This calls for strong encryption schemes that allow operations on data in an encrypted format without compromising the encryption. This paper presents an asymmetric multi-key and partially homomorphic encryption scheme. The scheme provides the addition operation by encrypting each decimal digit of the given integer number separately using a special key. In addition, data integrity processes are performed when an untrusted third party performs homomorphic operations on encrypted data. The proposed work considers the most widely known issues like the encrypted data size, slow operations at the hardware level, and high computing costs at the provider level. The size of generated ciphertext is almost equal to the size of the plaintext, and order-preserving is ensured using an asymmetrical encryption version.
A Top-Down Approach Based on the Circularity Potential to Increase the Use of Reclaimed Asphalt
Authors: Mantalovas Konstantinos , Dunn Iain Peter , Acuto Francesco , Vijayan Vineesh , Inzerillo Laura , Di Mino Gaetano
Published: April 2023

Resource depletion and climate change, amongst others, are increasingly worrying environmental challenges for which the road engineering sector is a major contributor. Globally, viable solutions that comply with the principles of circular economy (CE) are being investigated that can replace conventional asphalt mixtures in a post-fossil fuel society. The use of reclaimed asphalt (RA) is a widely used and well-established method to reduce the environmental and economic impacts of asphalt mixtures while increasing their circularity. However, RA’s market supply and demand have not yet been systematically analyzed and established. Moreover, the actual circularity potential and the opportunity of re-circulating RA in a closed-loop model have not yet been methodically defined. To address this, a three-layered framework to quantify and assess the circularity potential (Ω) of RA has been developed. To give stakeholders and legislative bodies a simple method to assess the opportunities available to them to become “more circular”, a novel equation has been formulated. This takes the form of a three-level indicator that considers: technical aspects, the effect of the RA market, and the legislative restrictions. A case study in Germany was structured and undertaken to develop and verify the proposed approach. The results indicate that the available RA is insufficient to cover the needs of asphalt mixture production; even though RA production is significantly lower than the actual need of asphalt mixtures, it is not utilized in its entirety. An impactful step forward is the alteration of the regulations to support the higher utilization of RA in asphalt mixtures, and subsequently, the increased circular opportunity and potential of RA. Thus, Circularity potential (Ω) is a composite indicator that can support stakeholders, designers, and asset managers during the process of decision-making, to follow more circular operational, design, and asphalt pavement management patterns.
Zn(II) Three-Dimensional Metal-Organic Frameworks Based on 2,5-Diiodoterephthalate and N,N Linkers: Structures and Features of Sorption Behavior
Authors: Zaguzin Alexander S. , Sukhikh Taisiya , Sokolov Maxim N. , Fedin Vladimir P. , Adonin Sergey A.
Published: April 2023

Two new coordination polymers based on Zn(II) and 2,5-diiodoterephthalate—{[Zn(2,5-I-bdc)bpe}] (1) and {[Zn(2,5-I-bdc)bpen}] (2)—were synthesized and characterized. Polymers 1 and 2 feature halogen bonding between the I atoms of MOF and DMF guest molecules, which plays a crucial role in structure stabilization. Selectivity of sorption towards different organic substrates was examined.
When One’s Not Enough: Colony Pool-Seq Outperforms Individual-Based Methods for Assessing Introgression in Apis mellifera mellifera
Authors: Buswell Victoria , Ellis Jonathan , Huml J. , Wragg David , Barnett Mark , Brown Andrew ,   The Scottish Beekeepers Association Citizen Science Group, Knight Mairi
Published: April 2023

The human management of honey bees (Apis mellifera) has resulted in the widespread introduction of subspecies outside of their native ranges. One well known example of this is Apis mellifera mellifera, native to Northern Europe, which has now been significantly introgressed by the introduction of C lineage honey bees. Introgression has consequences for species in terms of future adaptive potential and long-term viability. However, estimating introgression in colony-living haplodiploid species is challenging. Previous studies have estimated introgression using individual workers, individual drones, multiple drones, and pooled workers. Here, we compare introgression estimates via three genetic approaches: SNP array, individual RAD-seq, and pooled colony RAD-seq. We also compare two statistical approaches: a maximum likelihood cluster program (ADMIXTURE) and an incomplete lineage sorting model (ABBA BABA). Overall, individual approaches resulted in lower introgression estimates than pooled colonies when using ADMIXTURE. However, the pooled colony ABBA BABA approach resulted in generally lower introgression estimates than all three ADMIXTURE estimates. These results highlight that sometimes one individual is not enough to assess colony-level introgression, and future studies that do use colony pools should not be solely dependent on clustering programs for introgression estimates.
Effect of Systemic Insecticides Applied via Drench on the Mortality of Diaphorina citri on Curry Leaf
Authors: Vieira Julia Gabriela Aleixo , Santana Emile Dayara Rabelo , Thiesen Leonardo Vinicius , Matioli Thaís Fagundes , Yamamoto Pedro Takao
Published: April 2023

Huanglongbing (HLB), the most serious disease in citriculture, is caused by the bacteria Candidatus Liberibacter spp., which is transmitted by the Asian citrus psyllid (ACP) Diaphorina citri. HLB is mainly controlled with insecticides, necessitating the development of alternative methods, e.g., the use of trap plants such as curry leaf Bergera koenigii, which is highly attractive to the ACP. We evaluated the effects of the main systemic insecticides used by citrus growers, applied via drench to adults of D. citri on the curry leaf tree. We tested the persistence of three pesticides: thiamethoxam, thiamethoxam + chlorantraniliprole, and imidacloprid in protected cultivation and the field condition at 7, 14, 28, 42, 56, 70, 98, and 154 days after the application. Different concentrations of insecticides containing the active ingredient thiamethoxam were tested on adults to determine the LC10 and LC50. Finally, we assessed the sublethal effects on the oviposition and development of D. citri. The insecticides controlled the adults for long periods. However, in the field experiment, from 42 days after application there was a decrease in mortality caused by pesticides applied via drench, while in the protected cultivation, mortality did not decline until the last day of evaluation. The median lethal concentration (LC50) for thiamethoxam was 0.031 g of active ingredient per plant, and for thiamethoxam in a mixture, the LC50 was 0.028 g a.i. per plant. In the experiment with sublethal doses, D. citri did not oviposit on the treated plants. Our findings suggest that the attract-and-kill system using the curry leaf tree and systemic insecticides is effective for the control of D. citri and contributes to the integrated management of HLB.
Effect of Ultraviolet-B Radiating Drosophila melanogaster as Host on the Quality of Trichopria drosophilae, a Pupal Parasitoid of Drosophila suzukii
Authors: Liu Xuxiang , Yang Yongbang , Fan Qingwen , Zhang Qinyuan , Ji Qinge
Published: April 2023

The pupal parasitoid, Trichopria drosophilae Perkins (Hymenoptera: Diapriidae), is an ectoparasitoid of the genus Drosophila with great potential for application in biological control based on its excellent control efficiency for Drosophila suzukii Matsumura (Diptera: Drosophilidae), and it has has even been commercialized by biofactories. Due to its characteristics of short life cycle, large number of offspring, easy rearing, rapid reproduction, and low cost, Drosophila melanogaster (Diptera: Drosophilidae) is currently being utilized as a host to mass produce T. drosophilae. To simplify the mass rearing process and omit the separation of hosts and parasitoids, ultraviolet-B (UVB) was used as an irradiation source to irradiate D. melanogaster pupae, and the effects on T. drosophilae were studied. The results showed that UVB radiation significantly reduces host emergence and affects the duration of parasitoid development (female: F0 increased from 21.50 to 25.80, F1 from 23.10 to 26.10; male: F0 decreased from 17.00 to 14.10, F1 from 17.20 to 14.70), which has great significance for the separation of hosts and parasitoids as well as of females and males. Of the various studied conditions, UVB irradiation was ideal when the host was supplied with parasitoids for 6 h. The selection test results showed that the female-to-male ratio of emerging parasitoids in this treatment was highest at 3.47. The no-selection test resulted in the highest rates of parasitization and parasitoid emergence rate, maximized inhibition of host development, and allowed the omission of the separation step. Finally, the results of the semi-field test showed that the parasitoids bred in this treatment could search for their hosts normally and could therefore be directly applied in the biological control of Drosophila pests in the field.
Calculating the Surface Layer Thickness and Surface Energy of Aircraft Materials
Authors: Yurov Victor M. , Goncharenko Vladimir I. , Oleshko Vladimir S. , Ryapukhin Anatoly V.
Published: April 2023

The surface layer determines the physical properties of aviation materials and, based on these properties, the calculation of surface energy anisotropy can be implemented. Moreover, the value of the surface energy determines the service time and the destruction of aircraft structures surface layer, while the surface layer thickness determines the distance at which this process usually takes place. In this work, a new atomically smooth crystal empirical model is built without considering the surface roughness. This model can be used to theoretically predict the surface energy anisotropy and surface layer thickness of metals and other compounds, in particular the aviation materials. The work shows that the surface layer of an atomically smooth metal, like other compounds, consists of two nanostructured layers: d(I) and d(II). Having sufficient accuracy, the proposed model would allow the prediction of aviation materials performance properties without the need for ultrahigh vacuum or other complicated theoretical methods to analyze the surfaces of nanosystem atomic structures.
Nkx2-5 Loss of Function in the His-Purkinje System Hampers Its Maturation and Leads to Mechanical Dysfunction
Authors: Choquet Caroline , Sicard Pierre , Vahdat Juliette , Nguyen Thi , Kober Frank , Varlet Isabelle , Bernard Monique , Richard Sylvain , Kelly Robert , Lalevée Nathalie , Miquerol Lucile
Published: April 2023

The ventricular conduction or His-Purkinje system (VCS) mediates the rapid propagation and precise delivery of electrical activity essential for the synchronization of heartbeats. Mutations in the transcription factor Nkx2-5 have been implicated in a high prevalence of developing ventricular conduction defects or arrhythmias with age. Nkx2-5 heterozygous mutant mice reproduce human phenotypes associated with a hypoplastic His-Purkinje system resulting from defective patterning of the Purkinje fiber network during development. Here, we investigated the role of Nkx2-5 in the mature VCS and the consequences of its loss on cardiac function. Neonatal deletion of Nkx2-5 in the VCS using a Cx40-CreERT2 mouse line provoked apical hypoplasia and maturation defects of the Purkinje fiber network. Genetic tracing analysis demonstrated that neonatal Cx40-positive cells fail to maintain a conductive phenotype after Nkx2-5 deletion. Moreover, we observed a progressive loss of expression of fast-conduction markers in persistent Purkinje fibers. Consequently, Nkx2-5-deleted mice developed conduction defects with progressively reduced QRS amplitude and RSR’ complex associated with higher duration. Cardiac function recorded by MRI revealed a reduction in the ejection fraction in the absence of morphological changes. With age, these mice develop a ventricular diastolic dysfunction associated with dyssynchrony and wall-motion abnormalities without indication of fibrosis. These results highlight the requirement of postnatal expression of Nkx2-5 in the maturation and maintenance of a functional Purkinje fiber network to preserve contraction synchrony and cardiac function.
Bempedoic Acid: An Emerging Therapy for Uncontrolled Low-Density Lipoprotein (LDL) Cholesterol
Authors: Pradhan Akshyaya , Bhandari Monika , Vishwakarma Pravesh , Singh Abhishek , Perrone Marco Alfonso , Sethi Rishi
Published: April 2023

Atherosclerotic cardiovascular disease (ASCVD) is a silent epidemic, which is progressing relentlessly across the globe. Developing countries such as India have a high prevalence of dyslipidemia and consequently a huge burden of coronary artery disease (CAD) and ASCVD. Low-density lipoprotein is regarded as the primary culprit in the genesis of ASCVD, and statins are the first line therapy for LDL-C lowering. Statin therapy has unequivocally demonstrated the benefit of lowering LDL-C in patients across the spectrum of CAD and ASCVD. Muscle symptoms and worsening of glycemic homeostasis could be challenges with statin therapy, especially with the use of high doses. A large fraction of patients are also unable to achieve their LDL goals with statins alone in clinical practice. Moreover, LDL-C goals have become aggressive over years, necessitating a combination of lipid lowering therapies. PCSK-9 inhibitors and Inclisiran have emerged as robust and safe lipid-lowering agents, but parenteral administration and high cost precludes their widespread use. Bempedoic acid is a novel lipid-lowering agent working upstream of statins by inhibiting the enzyme ATP citrate lyase (ACL). The drug produces an average LDL lowering of 22–28% in statin-naïve patients and 17–18% when given to preexisting statin users. Because skeletal muscles lack the ACL enzyme, there is minimal risk of muscle-related symptoms. In combination with ezetimibe, the drug synergistically reduced LDL-C by 39%. Moreover, the drug has no adverse effect on glycemic parameters and lowers hsCRP (inflammation) like statin. The series of four randomized CLEAR trials, involving >4000 patients, have shown consistent LDL lowering across the spectrum of ASCVD patients with or without background therapy. The large and only cardiovascular outcome trial of the drug (CLEAR Outcomes) has recently demonstrated a 13% reduction of MACE at 40 months. Rise in levels of uric acid (four times) and acute gout (three times) are more common compared to placebo with the drug, owing to competitive renal transportation by OAT 2. In a nutshell, Bempedoic acid represents a value addition to the inventory of dyslipidemia management.
Correction: Oweira et al. Kynurenine Is the Main Metabolite of Tryptophan Degradation by Tryptophan 2,3-Dioxygenase in HepaRG Tumor Cells. J. Clin. Med. 2022, 11, 4794
Authors: Oweira Hani , Lahdou Imad , Mehrle Stefan , Khajeh Elias , Nikbakhsh Rajan , Ghamarnejad Omid , Terness Peter , Reißfelder Christoph , Sadeghi Mahmoud , Ramouz Ali
Published: April 2023

There was an error in the original publication [...]
Antibacterial Surgical Sutures Developed Using Electrostatic Yarn Wrapping Technology
Authors: Lou Ching-Wen , Hung Chun-Yu , Wei Mengdan , Li Tingting , Shiu Bing-Chiuan , Lin Jia-Horng
Published: April 2023

A significant amount of research has been conducted on applying functional materials as surgical sutures. Therefore, research on how to solve the shortcomings of surgical sutures through available materials has been given increasing attention. In this study, hydroxypropyl cellulose (HPC)/PVP/zinc acetate nanofibers were coated on absorbable collagen sutures using an electrostatic yarn winding technique. The metal disk of an electrostatic yarn spinning machine gathers nanofibers between two needles with positive and negative charges. By adjusting the positive and negative voltage, the liquid in the spinneret is stretched into fibers. The selected materials are toxicity free and have high biocompatibility. Test results indicate that the nanofiber membrane comprises evenly formed nanofibers despite the presence of zinc acetate. In addition, zinc acetate can effectively kill 99.9% of E. coli and S. aureus. Cell assay results indicate that HPC/PVP/Zn nanofiber membranes are not toxic; moreover, they improve cell adhesion, suggesting that the absorbable collagen surgical suture is profoundly wrapped in a nanofiber membrane that exerts antibacterial efficacy and reduces inflammation, thus providing a suitable environment for cell growth. The employment of electrostatic yarn wrapping technology is proven effective in providing surgical sutures with antibacterial efficacy and a more flexible range of functions.
Surface Modification of Biomedical Ti-18Zr-15Nb Alloy by Atomic Layer Deposition and Ag Nanoparticles Decoration
Authors: Konopatsky Anton , Teplyakova Tatyana , Sheremetyev Vadim , Yakimova Tamara , Boychenko Olga , Kozik Marina , Shtansky Dmitry , Prokoshkin Sergey
Published: April 2023

Superelastic biocompatible alloys attract significant attention as novel materials for bone tissue replacement. These alloys are often composed of three or more components that lead to the formation of complex oxide films on their surfaces. For practical use, it is desirable to have a single-component oxide film with a controlled thickness on the surface of biocompatible material. Herein we investigate the applicability of the atomic layer deposition (ALD) technique for surface modification of Ti-18Zr-15Nb alloy with TiO2 oxide. It was found that a 10–15 nm thick, low-crystalline TiO2 oxide layer is formed by ALD method over the natural oxide film (~5 nm) of the Ti-18Zr-15Nb alloy. This surface consists of TiO2 exclusively without any additions of Zr or Nb oxides/suboxides. Further, the obtained coating is modified by Ag nanoparticles (NPs) with a surface concentration up to 1.6% in order to increase the material’s antibacterial activity. The resulting surface exhibits enhanced antibacterial activity with an inhibition rate of more than 75% against E. coli bacteria.
Fiber-Type-Specific Hypertrophy with the Use of Low-Load Blood Flow Restriction Resistance Training: A Systematic Review
Authors: Schoenfeld Brad J. , Ogborn Dan , Piñero Alec , Burke Ryan , Coleman Max , Rolnick Nicholas
Published: April 2023

Emerging evidence indicates that the use of low-load resistance training in combination with blood flow restriction (LL-BFR) can be an effective method to elicit increases in muscle size, with most research showing similar whole muscle development of the extremities compared to high-load (HL) training. It is conceivable that properties unique to LL-BFR such as greater ischemia, reperfusion, and metabolite accumulation may enhance the stress on type I fibers during training compared to the use of LLs without occlusion. Accordingly, the purpose of this paper was to systematically review the relevant literature on the fiber-type-specific response to LL-BFR and provide insights into future directions for research. A total of 11 studies met inclusion criteria. Results of the review suggest that the magnitude of type I fiber hypertrophy is at least as great, and sometimes greater, than type II hypertrophy when performing LL-BFR. This finding is in contrast to HL training, where the magnitude of type II fiber hypertrophy tends to be substantially greater than that of type I myofibers. However, limited data directly compare training with LL-BFR to nonoccluded LL or HL conditions, thus precluding the ability to draw strong inferences as to whether the absolute magnitude of type I hypertrophy is indeed greater in LL-BFR vs. traditional HL training. Moreover, it remains unclear as to whether combining LL-BFR with traditional HL training may enhance whole muscle hypertrophy via greater increases in type I myofiber cross-sectional area.
Overconfidence in the Cognitive Reflection Test: Comparing Confidence Resolution for Reasoning vs. General Knowledge
Authors: Mata André
Published: April 2023

This research examines the metacognitive awareness that people have about their reasoning performance in the Cognitive Reflection Test (CRT). The first two studies compare confidence judgments about the CRT vs. general knowledge (GK) questions. Results show that (1) people are generally able to discriminate between correct and incorrect answers, but this ability is far from perfect, and it is greater for GK questions than for CRT problems. Indeed, and strikingly, (2) incorrect responses to CRT problems are produced with approximately the same level of confidence as correct responses to GK questions. However, (3) even though confidence is high for incorrect responses to CRT problems, it is even higher for correct responses. The results of two additional studies show that these differences in confidence are ultimately related to the conflict that CRT problems pose between intuition and deliberation. These findings have implications for the possibility of implicit error monitoring and dual-process models of overconfidence.
How Efficient Is Model-to-Model Data Assimilation at Mitigating Atmospheric Forcing Errors in a Regional Ocean Model?
Authors: Shapiro Georgy I. , Salim Mohammed
Published: April 2023

This paper examines the efficiency of a recently developed Nesting with Data Assimilation (NDA) method at mitigating errors in heat and momentum fluxes at the ocean surface coming from external forcing. The analysis uses a set of 19 numerical simulations, all using the same ocean model and exactly the same NDA process. One simulation (the reference) uses the original atmospheric data, and the other eighteen simulations are performed with intentionally introduced perturbations in the atmospheric forcing. The NDA algorithm uses model-to-model data assimilation instead of assimilating observations directly. Therefore, it requires a good quality, although a coarser resolution data assimilating parent model. All experiments are carried out in the South East Arabian Sea. The variables under study are sea surface temperature, kinetic energy, relative vorticity and enstrophy. The results show significant improvement in bias, root-mean-square-error, and correlation coefficients between the reference and the perturbed models when they are run in the data assimilating configurations. Residual post-assimilation uncertainties are similar or lower than uncertainties of satellite based observations. Different length of DA cycle within a range from 1 to 8 days has little effect on the accuracy of results.
An Integrated Bayesian Risk Model for Coastal Flow Slides Using 3-D Hydrodynamic Transport and Monte Carlo Simulation
Authors: Durap Ahmet , Balas Can Elmar , Çokgör Şevket , Balas Egemen Ander
Published: April 2023

The literature suggests two forms of flow slides: breaching and liquefaction. Both forms of failure have comparable ultimate circumstances, but the progression and sand movement mechanisms of breaching failure diverge from those of liquefaction. The first type, breaching, occurs in densely packed sand and is characterized by slow sand grain discharge throughout the dilation of the failing soil particles and negative excess pore pressures. The latter form, known as liquefaction, is the process by which a mass of soil abruptly begins to behave like a flowing liquid, and as a result, it can flow out across overly mild slopes. The process begins in compacted sand and is linked to positive surplus pore water pressures that are caused by the compaction of the sand. Despite the available literature on flow slide failures, our understanding of the mechanisms involved remains limited. Since flow slides often begin below the water surface, they can go undetected until the collapse reaches the bank above ground. The complexity of flow slides requires the use of cutting-edge technological instruments, diving equipment, advanced risk assessment, and a variety of noteworthy probabilistic and sensitivity analyses. Hence, we developed a new sensitivity index to identify the risk of breach failure and vulnerable coastal areas to this risk. In addition, we developed a sophisticated hybrid model that allows for all possibilities of flow slides in sync with random variables used in this new sensitivity index. In this new hybrid model, three distinctive models exist. The 3D Hydrodynamic Model addresses waves, wind, current, climate change, and sediment transport. The Monte Carlo Simulation is responsible for sensitivity analysis, and the Bayesian Network focuses on joint probabilities of coastal flow slide parameters of this new index that incorporates all environmental parameters, including climate change. With the assistance of these three models, researchers aim to: (a) expand the application scope by presenting a method on coastal flow slides; (b) consider different particle diameters corresponding to critical angle slope failure; (c) analyze variables that can play a pivotal role in the flow slides; and (d) present a methodology for coupling coastal flow slide projections with reliable outcomes. The hybrid model incorporates random variables of retrogressive breach failures, and the new risk index considers their ranges to control the simulation. The use of such a hybrid model and risk index offers a robust and computationally efficient approach to evaluating coastal flow slides.
Sea-Level Rise Effects on Changing Hazard Exposure to Far-Field Tsunamis in a Volcanic Pacific Island
Authors: Welsh Rebecca , Williams Shaun , Bosserelle Cyprien , Paulik Ryan , Chan Ting Josephina , Wild Alec , Talia Lameko
Published: April 2023

Coastal flooding exacerbated by climate change is recognised as a major global threat which is expected to impact more than a quarter of all people currently residing in Pacific Island countries. While most research in the last decade has focused on understanding the dynamics and impacts of future coastal flooding from extreme sea levels, the effects of relative sea level rise (RSLR) on exacerbating tsunami hazards are not well understood. Far-field or distant sourced tsunamis tend to have relatively lower impacts in Pacific Island states compared with locally sourced events, but there is limited understanding of how the impact of far-field tsunamis changes over time due to RSLR. Using the hydrodynamics software BG-Flood, we modelled the Tōhoku-oki tsunami from propagation to inundation in Samoa under incremental SLR to examine the effects that RSLR has on changing the exposure of the built environment (e.g., buildings) to a far-field tsunami. Outputs of maximum tsunami inundation and flow depth intensities which incorporate incremental SLR were then combined with digital representations of buildings and depth-damage functions in the RiskScape multi-hazard risk modelling software to assess the changes in building exposure over time. Results suggest that the impacts of Tōhoku-oki-type far-field tsunamis become significant once RSLR reaches 1 m above present levels. Present-day building exposure will increase by approx. 500% with 1 m RSLR by 2080–2130, and approx. 2350% with 2 m RSLR by as early as 2130–2140. These findings provide useful insights for application to tsunami hazard risk assessments under changing sea level conditions in analogous island environments.
Mycotic Diseases in Chelonians
Authors: Nardoni Simona , Mancianti Francesca
Published: April 2023

Turtles and ‘tortoises’ populations are declining in number, the factors driving extinction risks being related to habitat loss and degradation, climate change, introduction of invasive plant and animal species, consumption by humans for food and medicinal use, and collection for international pet trade. Fungal infections represent one of the main threats for ecosystem health. The present narrative review deals with conventional and emerging mycoses of Chelonians. Although conventional mycoses in captive and pet reptiles would depend on poor husbandry, being the agents mostly opportunistic pathogens, some fungal species were reported to occur more frequently, such as the entomopathogen Purpureocillium lilacinum. Furthermore, emerging agents such as the Fusarium solani species complex have been recognized as a real threat for the surviving of some aquatic species, acting as primary pathogens. This complex has been recently included within pathogens in One Health issues. Emydomyces testavorans is recognized as an emerging threat, although, due its recent identification, information about its epidemiology is limited. Data about treatments and outcomes of mycoses in Chelonians are also referred.
A Novel Effector FlSp1 Inhibits the Colonization of Endophytic Fusarium lateritium and Increases the Resistance to Ralstonia solanacearum in Tobacco
Authors: Huang Jianming , He Zhangjiang , Wang Jiankang , Zha Xingping , Xiao Qing , Liu Guihua , Li Yongjie , Kang Jichuan
Published: April 2023

Effectors are crucial for the interaction between endophytes and their host plants. However, limited attention has been paid to endophyte effectors, with only a few reports published. This work focuses on an effector of Fusarium lateritium, namely FlSp1 (Fusarium-lateritium-Secreted-Protein), a typical unknown secreted protein. The transcription of FlSp1 was up-regulated after 48 h following fungal inoculation in the host plant, i.e., tobacco. The inactivation of FlSp1 with the inhibition rate decreasing by 18% (p < 0.01) resulted in a remarkable increase in the tolerance of F. lateritium to oxidative stress. The transient expression of FlSp1 stimulated the accumulation of reactive oxygen species (ROS) without causing plant necrosis. In comparison with the wild type of F. lateritium (WT), the FlSp1 mutant of the F. lateritium plant (ΔFlSp1) reduced the ROS accumulation and weakened the plant immune response, which resulted in significantly higher colonization in the host plants. Meanwhile, the resistance of the ΔFlSp1 plant to the pathogenic Ralstonia solanacearum, which causes bacterial wilt, was increased. These results suggest that the novel secreted protein FlSp1 might act as an immune-triggering effector to limit fungal proliferation by stimulating the plant immune system through ROS accumulation and thus balance the interaction between the endophytic fungi and their host plants.
Genomic and Transcriptomic Survey Provides Insights into Molecular Basis of Pathogenicity of the Sunflower Pathogen Phoma macdonaldii
Authors: Chen Xuejing , Hao Xiaoran , Akhberdi Oren , Zhu Xudong
Published: April 2023

Phoma macdonaldii (teleomorph Leptosphaeria lindquistii) is the causal agent of sunflower (Helianthus annuus L.) black stem. In order to investigate the molecular basis for the pathogenicity of P. ormacdonaldii, genomic and transcriptomic analyses were performed. The genome size was 38.24 Mb and assembled into 27 contigs with 11,094 putative predicted genes. These include 1133 genes for CAZymes specific for plant polysaccharide degradation, 2356 for the interaction between the pathogen and host, 2167 for virulence factors, and 37 secondary metabolites gene clusters. RNA-seq analysis was conducted at the early and late stages of the fungal spot formation in infected sunflower tissues. A total of 2506, 3035, and 2660 differentially expressed genes (DEGs) between CT and each treatment group (LEAF-2d, LEAF-6d, and STEM) were retrieved, respectively. The most significant pathways of DEGs from these diseased sunflower tissues were the metabolic pathways and biosynthesis of secondary metabolites. Overall, 371 up-regulated DEGs were shared among LEAF-2d, LEAF-6d, and STEM, including 82 mapped to DFVF, 63 mapped to PHI-base, 69 annotated as CAZymes, 33 annotated as transporters, 91 annotated as secretory proteins, and a carbon skeleton biosynthetic gene. The most important DEGs were further confirmed by RT-qPCR. This is the first report on the genome-scale assembly and annotation for P. macdonaldii. Our data provide a framework for further revealing the underlying mechanism of the pathogenesis of P. macdonaldii, and also suggest the potential targets for the diseases caused by this fungal pathogen.
Sesquiterpenes from the Fungus Antrodiella albocinnamomea with Cytotoxicity and Antibacterial Activity
Authors: Ning Jinlei , Wu Feng , Liu Jikai , He Juan , Feng Tao
Published: April 2023

Eight new sesquiterpenes, namely, albocinnamins A−H (1−8), along with two known ones (9 and 10), have been isolated from the fungus Antrodiella albocinnamomea. Compound 1 possesses a new backbone that might be derived from cadinane-type sesquiterpene. Structures of the new compounds were elucidated by detailed spectroscopic data analysis, single-crystal X-ray diffraction, and ECD calculations. Compounds 1a and 1b showed cytotoxicity against SW480 and MCF-7 cells, with IC50 values ranging from 19.3 to 33.3 μM, while compound 2 displayed cytotoxicity against the HL-60 cell with an IC50 value of 12.3 μM. In addition, compounds 5 and 6 exhibited antibacterial activity against Staphylococcus aureus with MIC values of 64 and 64 µg/mL, respectively.
Genome Sequencing and Analysis Reveal Potential High-Valued Metabolites Synthesized by Lasiodiplodia iranensis DWH-2
Authors: Li Ruiying , Zheng Pu , Sun Xingyun , Dong Wenhua , Shen Ziqiang , Chen Pengcheng , Wu Dan
Published: April 2023

Lasiodiplodia sp. is a typical opportunistic plant pathogen, which can also be classified as an endophytic fungus. In this study, the genome of a jasmonic-acid-producing Lasiodiplodia iranensis DWH-2 was sequenced and analyzed to understand its application value. The results showed that the L. iranensis DWH-2 genome was 43.01 Mb in size with a GC content of 54.82%. A total of 11,224 coding genes were predicted, among which 4776 genes were annotated based on Gene Ontology. Furthermore, the core genes involved in the pathogenicity of the genus Lasiodiplodia were determined for the first time based on pathogen–host interactions. Eight Carbohydrate-Active enzymes (CAZymes) genes related to 1,3-β-glucan synthesis were annotated based on the CAZy database and three relatively complete known biosynthetic gene clusters were identified based on the Antibiotics and Secondary Metabolites Analysis Shell database, which were associated with the synthesis of 1,3,6,8-tetrahydroxynaphthalene, dimethylcoprogen, and (R)-melanin. Moreover, eight genes associated with jasmonic acid synthesis were detected in pathways related to lipid metabolism. These findings fill the gap in the genomic data of high jasmonate-producing strains.
Regulation of Intracellular Reactive Oxygen Species Levels after the Development of Phallus rubrovolvatus Rot Disease Due to Trichoderma koningii Mycoparasitism
Authors: Lu Meiling , Wen Tingchi , Guo Ming , Li Qihua , Peng Xingcan , Zhang Yan , Lu Zhenghua , Wang Jian , Xu Yanjun , Zhang Chao
Published: April 2023

Phallus rubrovolvatus is a unique mushroom used for medicinal and dietary purposes in China. In recent years, however, the rot disease of P. rubrovolvatus has seriously affected its yield and quality, becoming an economically important threat. In this study, samples of symptomatic tissues were collected, isolated, and identified from five major P. rubrovolvatus production regions in Guizhou Province, China. Based on combined analyses of phylogenies (ITS and EF1-α), morphological characteristics and Koch’s postulates, Trichoderma koningiopsis and Trichoderma koningii were identified as the pathogenic fungal species. Among these, T. koningii exhibited stronger pathogenicity than the other strains; thus, T. koningii was used as the test strain in the follow-up experiments. Upon co-culturing T. koningii with P. rubrovolvatus, the hyphae of the two species were intertwined, and the color of the P. rubrovolvatus hyphae changed from white to red. Moreover, T. koningii hyphae were wrapped around P. rubrovolvatus hyphae, leading to their shortening and convolution and ultimately inhibiting their growth due to wrinkling; T. koningii penetrated the entire basidiocarp tissue of P. rubrovolvatus, causing serious damage to the host basidiocarp cells. Further analyses revealed that T. koningii infection resulted in the swelling of basidiocarps and significantly enhanced the activity of defense-related enzymes, such as malondialdehyde, manganese peroxidase, and polyphenol oxidase. These findings offer theoretical support for further research on the infection mechanisms of pathogenic fungi and the prevention of diseases caused by them.
Exposure–Response Analysis of the Sodium–Glucose Cotransporter-2 Inhibitors Dapagliflozin and Empagliflozin on Kidney Hemodynamics in Patients with Type 2 Diabetes
Authors: van der Hoek Sjoukje , Koomen Jeroen V. , van Bommel Erik J. M. , Mosterd Charlotte M. , Scholtes Rosalie A. , Hesp Anne C. , Stevens Jasper , van Raalte Daniel H. , Heerspink Hiddo J. L.
Published: April 2023

Sodium–glucose cotransporter-2 (SGLT2) inhibitors improve markers for renal and cardiovascular outcomes in patients with and without type 2 diabetes (T2D). To assess whether individual differences in plasma drug exposure can explain inter-individual response variation, we characterized the exposure–response relationship for two SGLT2 inhibitors on several clinical and kidney hemodynamic variables. Data were obtained from two studies, RED and RECOLAR, assessing the effects of once-daily 10 mg dapagliflozin or empagliflozin, respectively, on kidney hemodynamics in patients with T2D. Individual plasma exposure was estimated using non-compartmental analyses and exposure–response relationships were assessed using linear mixed-effects models. In 23 patients participating in RED, the dapagliflozin geometric mean apparent area under the concentration-time curve during one dosing interval at steady state (AUC0–tau,ss) was 1153.1 µg/L*h (coefficient of variation (CV) 81.8%) and associated, per doubling, with decreases in body weight (0.29 kg, p < 0.001), systolic blood pressure (0.80 mmHg, p = 0.002), measured glomerular filtration rate (mGFR) (0.83 mL/min, p = 0.03), and filtration fraction (0.09%, p = 0.04). In 20 patients participating in RECOLOR, the empagliflozin geometric mean AUC0–tau,ss was 2035.7 nmol/L*h (CV 48.4%) and associated, per doubling, with decreases in body weight (0.13 kg, p = 0.002), systolic blood pressure (0.65 mmHg, p = 0.045), and mGFR (0.78 mL/min, p = 0.002). To conclude, dapagliflozin and empagliflozin plasma exposure was highly variable between patients and associated with inter-individual variation in response variables.
The Evaluation of Cartilage Regeneration Efficacy of Three-Dimensionally Biofabricated Human-Derived Biomaterials on Knee Osteoarthritis: A Single-Arm, Open Label Study in Egypt
Authors: Abdelhamid Mohamed M. , Eid Gaber , Othman Moustafa H. M. , Ibrahim Hamdy , Elsers Dalia , Elyounsy Mohamed , Kwon Soon Yong , Kim Minju , Kim Doheui , Kim Jin-Wook , Ryu Jina , El-Radi Mohamed Abd , Fetih Tarek N.
Published: April 2023

Full thickness cartilage defects in cases of knee osteoarthritis are challenging in nature and are difficult to treat. The implantation of three-dimensional (3D) biofabricated grafts into the defect site can be a promising biological one-stage solution for such lesions that can avoid different disadvantages of the alternative surgical treatment options. In this study, the short-term clinical outcome of a novel surgical technique that uses a 3D bioprinted micronized adipose tissue (MAT) graft for knee cartilage defects is assessed and the degree of incorporation of such graft types is evaluated via arthroscopic and radiological analyses. Ten patients received 3D bioprinted grafts consisting of MAT with an allogenic hyaline cartilage matrix on a mold of polycaprolactone, with or without adjunct high tibial osteotomy, and they were monitored until 12 months postoperatively. Clinical outcomes were examined with patient-reported scoring instruments that consisted of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS). The graft incorporation was assessed using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. At 12 months follow-up, cartilage tissue biopsy samples were taken from patients and underwent histopathological examination. In the results, at final follow-up, the WOMAC and KOOS scores were 22.39 ± 7.7 and 79.16 ± 5.49, respectively. All scores were significantly increased at final follow-up (p < 0.0001). MOCART scores were also improved to a mean of 82.85 ± 11.49, 12 months after operation, and we observed a complete incorporation of the grafts with the surrounding cartilage. Together, this study suggests a novel regeneration technique for the treatment of knee osteoarthritis patients, with less rejection response and better efficacy.